Browsing by Author "Sharma, Uttam"

Now showing 1 - 20 of 24

Ampelopsin targets in cellular processes of cancer: Recent trends and advances
(Elsevier Inc., 2022-07-27T00:00:00) Tuli, Hardeep Singh; Sak, Katrin; Garg, Vivek Kumar; Kumar, Ajay; Adhikary, Shubham; Kaur, Ginpreet; Parashar, Nidarshana Chaturvedi; Parashar, Gaurav; Mukherjee, Tapan Kumar; Sharma, Uttam; Jain, Aklank; Mohapatra, Ranjan K.; Dhama, Kuldeep; Kumar, Manoj; Singh, Tejveer
Cancer is being considered as a serious threat to human health globally due to limited availability and efficacy of therapeutics. In addition, existing chemotherapeutic drugs possess a diverse range of toxic side effects. Therefore, more research is welcomed to investigate the chemo-preventive action of plant-based metabolites. Ampelopsin (dihydromyricetin) is one among the biologically active plant-based chemicals with promising anti-cancer actions. It modulates the expression of various cellular molecules that are involved in cancer progressions. For instance, ampelopsin enhances the expression of apoptosis inducing proteins. It regulates the expression of angiogenic and metastatic proteins to inhibit tumor growth. Expression of inflammatory markers has also been found to be suppressed by ampelopsin in cancer cells. The present review article describes various anti-tumor cellular targets of ampelopsin at a single podium which will help the researchers to understand mechanistic insight of this phytochemical. � 2022 The Authors
Application of curcumin nanoformulations to target folic acid receptor in cancer: Recent trends and advances
(Academic Press Inc., 2023-06-20T00:00:00) Hussain, Arif; Kumar, Ajay; Uttam, Vivek; Sharma, Uttam; Sak, Katrin; Saini, Reena V.; Saini, Adesh K.; Haque, Shafiul; Tuli, Hardeep Singh; Jain, Aklank; Sethi, Gautam
Curcumin, derived from turmeric, has a strong anticancer potential known for millennia. The development of this phytochemical as a medicine has been hampered by several significant deficiencies, including its poor water solubility and low bioavailability. This review article discusses possibilities to overcome these bottlenecks by focusing on this natural polyphenol's nanoformulation. Moreover, preparation of curcumin conjugates containing folates as ligands for folic acid receptors can add a new important dimension in this field, allowing specific targeting of cancer cells, considering the significantly higher expression of these receptors in malignant tissues compared to normal cells. It is highly expected that simultaneous improvement of different aspects of curcumin in fighting against such a complex and multifaceted disease like cancer. Therefore, we can better comprehend cancer biology by developing a mechanistic understanding of curcumin, which will also inspire the scientific community to develop new pharmacological models, and exploration of emerging directions to revitalize application of natural products in cancer therapy. � 2023 Elsevier Inc.
Biosynthesis of Zinc Oxide Nanoparticles Using Catharanthus Roseus Leaves and Their Therapeutic Response in Breast Cancer (MDA-MB-231) Cells
(Routledge, 2021-07-26T00:00:00) Bangroo, Apoorva; Malhotra, Akshay; Sharma, Uttam; Jain, Aklank; Kaur, Anupreet
As the current study reports the utilization of the leaf extract of Catharanthus roseus (C.roseus) for the biological synthesis of zinc oxide nanoparticles (ZnO NPs) because of the importance of the importance of health and environment. Bioinspired synthesis were characterized using Fourier Transform Infrared Spectroscopy (FT-IR), Field Emission-Scanning Electron Microscopy (FE-SEM), Transmission Electron Microscopy (TEM), Energy-Dispersive X-ray Spectroscopy (EDX) and X-Ray diffraction (XRD). XRD and TEM micrograph analysis revealed that the synthesized nanostructures were well-dispersed and spherical with the average particle size in the 18-30 nm range were produced. The FT-IR spectra confirmed presence of phenolic compounds that act as reducing and capping agents. Further, it suggested the possible utilization of hydroxyl groups and amides in the reduction of Zn ions and stablization of ZnO NPs. Zinc oxide nanomaterials are effective in cancer treatments, including the destruction of tumor cells with minimal damage to healthy cells. The toxicity of zinc oxide nanomaterials was checked in vitro in the human breast cancer line MDA-MB-231. Inverse relation of the percentage of viable cells to the concentration of zinc oxide nanomaterials at increasing molar levels was assessed. The cytotoxicity analysis used in the MTT test shows the substantial viable MDA-MB-231-cells despite the increased concentration of exposure to zinc oxide nanomaterials. Reduction in the ratio of viable MDA-MB-231 cells after being exposed to zinc oxide nanomaterials was compared to untreated cancerous cells. The present approach to biosynthesis is quick, inexpensive, eco-friendly, and high-rise stable nanomaterials of zinc oxide with substantial cancer potential. This is the first study that reports molar concentrations (with the lowest concentration of 10 mM) as an anticancer agent for breast cancer and potential clinical uses for synthesized zinc oxide nanomaterials. Thus, C. roseus based synthesized ZnO NPs could be explored not only as environmentally benign method but also as a potential anti-carcinogenic agent. � 2022 Taylor & Francis Group, LLC.
Circulating long non-coding RNA EWSAT1 acts as a liquid biopsy marker for esophageal squamous cell carcinoma: A pilot study
(KeAi Communications Co., 2023-10-28T00:00:00) Uttam, Vivek; Rana, Manjit Kaur; Sharma, Uttam; Singh, Karuna; Jain, Aklank
The widespread public health problem of esophageal squamous cell carcinoma (ESCC) is the cause of an increasing number of deaths each year due to delayed diagnosis. Therefore, we require specific and sensitive new biomarkers to manage ESCC better. The detection of diseases, such as cancer, can now be achieved through non-invasive circulating blood-based methods. Blood-based circulating non-coding RNAs, such as miRNA and lncRNA, have been extensively used as valuable markers for lung, esophageal, and breast cancer diagnostic purposes, as quoted in our previous research. Herein, we investigated the role of novel long non-coding RNA EWSAT1 as a blood-based liquid biopsy biomarker for the ESCC. Our findings indicate that EWSAT1 lncRNA has an increased tumor suppressive activity in ESCC, as it reduces by ?2.59-fold relative to healthy controls. Moreover, we established that EWSAT1 expression can significantly distinguish between clinicopathological characteristics, including age, gender, and lifestyle choices such as smoking, alcohol consumption, and drinking hot beverages among patients with ESCC and healthy individuals. In addition, the expression levels of lncRNA EWSAT1 could distinguish between individuals with more advanced ESCC cancer and those without it, as illustrated by the ROC curve (AUC = 0.7174, 95 % confidence intervals = 0.5901 to 0.8448, p-value = 0.001). Our in-silico prediction methods demonstrated that miR-873-5p is the direct target of EWSAT1, which competes with the tumor suppressor candidate 3 (TUSC3) and EGL-9 family hypoxia-inducible factor 3 (EGLN3) mRNAs through a sponging mechanism, creating the EWSAT1/miR-873-5p/mRNA axis. We have analyzed the role of EWSAT1 in various cellular processes and signaling pathways, including mTOR, Wnt, and MAPK signaling pathways. Circulating EWSAT1 can be used as a liquid biopsy marker for diagnosis of ESCC and has the potential to serve as an effective therapeutic biomarker, according to this pilot study. � 2023 The Authors
Circulating Long Non-Coding RNAs LINC00324 and LOC100507053 as Potential Liquid Biopsy Markers for Esophageal Squamous Cell Carcinoma: A Pilot Study
(Frontiers Media S.A., 2022-02-14T00:00:00) Sharma, Uttam; Barwal, Tushar Singh; Khandelwal, Akanksha; Rana, Manjit Kaur; Rana, Amrit Pal Singh; Singh, Karuna; Jain, Aklank
Background: Despite the availability of advanced technology to detect and treat esophageal squamous cell carcinoma (ESCC), the 5-year survival rate of ESCC patients is still meager. Recently, long non-coding RNAs (lncRNAs) have emerged as essential players in the diagnosis and prognosis of various cancers. Objective: This pilot study focused on identifying circulating lncRNAs as liquid biopsy markers for the ESCC. Methodology: We performed next-generation sequencing (NGS) to profile circulating lncRNAs in ESCC and healthy individuals� blood samples. The expression of the top five upregulated and top five downregulated lncRNAs were validated through quantitative real-time PCR (qRT-PCR), including samples used for the NGS. Later, we explored the diagnostic/prognostic potential of lncRNAs and their impact on the clinicopathological parameters of patients. To unravel the molecular target and pathways of identified lncRNAs, we utilized various bioinformatics tools such as lncRnome, RAID v2.0, Starbase, miRDB, TargetScan, Gene Ontology, and KEGG pathways. Results: Through NGS profiling, we obtained 159 upregulated, 137 downregulated, and 188 neutral lncRNAs in ESCC blood samples compared to healthy individuals. Among dysregulated lncRNAs, we observed LINC00324 significantly upregulated (2.11-fold; p-value = 0.0032) and LOC100507053 significantly downregulated (2.22-fold; p-value = 0.0001) in ESCC patients. Furthermore, we found LINC00324 and LOC100507053 could discriminate ESCC cancer patients� from non-cancer individuals with higher accuracy of Area Under the ROC Curve (AUC) = 0.627 and 0.668, respectively. The Kaplan-Meier and log-rank analysis revealed higher expression levels of LINC00324 and lower expression levels of LOC100507053 well correlated with the poor prognosis of ESCC patients with a Hazard ratio of LINC00324 = 2.48 (95% CI: 1.055 to 5.835) and Hazard ratio of LOC100507053 = 4.75 (95% CI: 2.098 to 10.76)]. Moreover, we also observed lncRNAs expression well correlated with the age (>50 years), gender (Female), alcohol, tobacco, and hot beverages consumers. Using bioinformatics tools, we saw miR-493-5p as the direct molecular target of LINC00324 and interacted with the MAPK signaling pathway in ESCC pathogenesis. Conclusion: This pilot study suggests that circulating LINC00324 and LOC100507053 can be used as a liquid biopsy marker of ESCC; however, multicentric studies are still warranted. Copyright � 2022 Sharma, Barwal, Khandelwal, Rana, Rana, Singh and Jain.
Circulating miR-320a Acts as a Tumor Suppressor and Prognostic Factor in Non-small Cell Lung Cancer
(Frontiers Media S.A., 2021-03-23T00:00:00) Khandelwal, Akanksha; Sharma, Uttam; Barwal, Tushar Singh; Seam, Rajeev Kumar; Gupta, Manish; Rana, Manjit Kaur; Vasquez, Karen M.; Jain, Aklank
Dysregulated expression profiles of microRNAs (miRNAs) have been observed in several types of cancer, including non-small cell lung cancer (NSCLC); however, the diagnostic and prognostic potential of circulating miRNAs in NSCLC remains largely undefined. Here we found that circulating miR-320a was significantly down-regulated (~5.87-fold; p < 0.0001) in NSCLC patients (n = 80) compared to matched control plasma samples from healthy subjects (n = 80). Kaplan-Meier survival analysis revealed that NSCLC patients with lower levels of circulating miR-320a had overall poorer prognosis and survival rates compared to patients with higher levels (p < 0.0001). Moreover, the diagnostic and prognostic potential of miR-320a correlated with clinicopathological characteristics such as tumor size, tumor node metastasis (TNM) stage, and lymph node metastasis. Functionally, depletion of miR-320a in human A549 lung adenocarcinoma cells induced their metastatic potential and reduced apoptosis, which was reversed by exogenous re-expression of miR-320a mimics, indicating that miR-320a has a tumor-suppressive role in NSCLC. These results were further supported by high levels of epithelial-mesenchymal transition (EMT) marker proteins (e.g., Beta-catenin, MMP9, and E-cadherin) in lung cancer cells and tissues via immunoblot and immunohistochemistry experiments. Moreover, through bioinformatics and dual-luciferase reporter assays, we demonstrated that AKT3 was a direct target of miR-320a. In addition, AKT3-associated PI3K/AKT/mTOR protein-signaling pathways were elevated with down-regulated miR-320a levels in NSCLC. These composite data indicate that circulating miR-320a may function as a tumor-suppressor miRNA with potential as a prognostic marker for NSCLC patients. � Copyright � 2021 Khandelwal, Sharma, Barwal, Seam, Gupta, Rana, Vasquez and Jain.
Clinical potential of long non-coding RNA LINC01133 as a promising biomarker and therapeutic target in cancers
(Newlands Press Ltd, 2022-02-23T00:00:00) Sharma, Uttam; Barwal, Tushar Singh; Murmu, Masang; Acharya, Varnali; Pant, Neha; Dey, Damayanti; Vivek; Gautam, Ashima; Bazala, Sonali; Singh, Ipsa; Azzouz, Farah; Bishayee, Anupam; Jain, Aklank
Recently, long intergenic non-protein coding RNA 01133 (LINC01133) was identified as a novel transcript in cancers. It modulates various hallmarks of cancers and acts as oncogenic in some cancers while tumor-suppressive in others. Furthermore, the expression of LINC01133 correlates with tumor size, advanced tumor node metastasis stage and lymphatic node metastasis, Ki-67 levels and overall survival of patients. Herein, the authors provide an in-depth analysis describing how LINC01133 modulates the multiple cancer-associated signaling pathways and the pathogenesis of various malignancies and treatment regimens. Based on the role played by LINC01133, the authors propose LINC01133 as both a potential biomarker and a therapeutic target in cancer. � 2022 Future Medicine Ltd.
Evolution of Frozen Section in Carcinoma Breast: Systematic Review
(Hindawi Limited, 2022-05-23T00:00:00) Rana, Manjit Kaur; Rana, Amrit Pal Singh; Sharma, Uttam; Barwal, Tushar Singh; Jain, Aklank
Background. The frozen section (FS) has been a good technique in surgical management of breast lesions since many years. But complete agreement and cooperation have not been achieved everywhere among surgeons and pathologists especially in the developing countries. FS undergoes continuous criticism due to various shortcomings but continued to be evaluated especially in developing countries. Objectives. This review was conducted to synthesize information on the use of frozen section in carcinoma breast. Data Sources. The MEDLINE database for frozen section since its origin and its implication in recent breast surgery techniques was studied. Study Eligibility Criteria. Sixty-five articles were reviewed with complete analysis on FS in both benign and malignant breast lesions. Study Appraisal and Synthesis Methods. The analysis of frozen section was done as a diagnostic tool in breast lesions, margin status in breast conservative surgery in carcinoma breast, and sentinel lymph node and use of immunohistochemistry for sentinel lymph node FS. Results. It was analysed that the FS gives accurate results in margin status analysis, decreasing rerecurrence. Conclusion. The accuracy of FSA, low recurrence rate, avoidance of reoperation, and good cosmesis are the key points of its use in breast conservative surgery. Its use in sentinel lymph node biopsy (SLNB) is equivocal. However, application of immunohistochemistry on frozen section of SLNB is an evolving trend in today's era. � 2022 Manjit Kaur Rana et al.
Expression analysis of long non-coding RNA GAS5 and BANCR in lung cancer cell line A549 compared to IMR-90.
(Central University of Punjab, 2018) Sharma, Uttam; Jain, Aklank
Lung cancer is the major cause of death worldwide. Several chemotherapeutic drugs and therapies have been established, but the early diagnosis and prognosis of lung cancer is still a question. Long non-coding RNAs are important regulator molecules in the human genome, which serves as transcriptional modulator, post transcriptional processor, chromatin remodeletor and splicing regulator during the gene modification process. Emerging studies have suggested the role of long noncoding RNA as potential biomarker for cancer diagnosis and prognosis by functioning as tumor suppressors and oncogenes. Several studies have been reported on cell lines, tissues as well as tumor and the molecular mechanism is still not clearly understood. GAS5 and BANCR are two long non-coding RNAs, which are found to be down-regulated in multiple cancers such as lung carcinoma, breast cancer, etc. In the current study, we focus on the expression analysis of GAS5 and BANCR in A549 cell line compared to IMR-90 cell line to study the role of long non-coding RNA in the pathogenesis of lung cancer. Furthermore, we investigated the expression of GAS5 and BANCR using quantitative Real-Time PCR. The result showed that GAS5 and BANCR expression was significantly down-regulated in cancerous cell line compared to non-cancerous cell line. The fold change of lncRNAs GAS5 and BANCR was 14 times (P=0.0088) and 7 times (P=0.0088) down-regulated in A549 cell line respectively. The melt curve analysis showed that there was only one sharp peak obtained for both GAS5 and BANCR i iv which suggests that primers bind to their specific targets and no primer dimer was observed.
Galangin: A metabolite that suppresses anti-neoplastic activities through modulation of oncogenic targets
(SAGE Publications Inc., 2021-12-14T00:00:00) Tuli, Hardeep Singh; Sak, Katrin; Adhikary, Shubham; Kaur, Ginpreet; Aggarwal, Diwakar; Kaur, Jagjit; Kumar, Manoj; Parashar, Nidarshana Chaturvedi; Parashar, Gaurav; Sharma, Uttam; Jain, Aklank
With the dramatic increase in cancer incidence all over the world in the last decades, studies on identifying novel efficient anti-cancer agents have been intensified. Historically, natural products have represented one of the most important sources of new lead compounds with a wide range of biological activities. In this article, the multifaceted anti-cancer action of propolis-derived flavonoid, galangin, is presented, discussing its antioxidant, anti-inflammatory, antiproliferative, pro-apoptotic, anti-angiogenic, and anti-metastatic effects in various cancer cells. In addition, co-effects with standard chemotherapeutic drugs as well as other natural compounds are also under discussion, besides highlighting modern nanotechnological advancements for overcoming the low bioavailability issue characteristic of galangin. Although further studies are needed for confirming the anti-cancer potential of galangin in vivo malignant systems, exploring this natural compound might open new perspectives in molecular oncology. � 2021 by the Society for Experimental Biology and Medicine.
The imminent role of microRNAs in salivary adenoid cystic carcinoma
(Neoplasia Press, Inc., 2022-11-04T00:00:00) Kumar, Pawan; Kumawat, Ram Kumar; Uttam, Vivek; Behera, Alisha; Rani, Medha; Singh, Neha; Barwal, Tushar Singh; Sharma, Uttam; Jain, Aklank
Unfortunately, despite the severe problem associated with salivary adenoid cystic carcinoma (SACC), it has not been studied in detail yet. Therefore, the time has come to understand the oncogenic cause of SACC and find the correct molecular markers for diagnosis, prognosis, and therapeutic target to tame this disease. Recently, we and others have suggested that non-coding RNAs, specifically microRNAs and long non-coding RNAs, can be ideal biomarkers for cancer(s) diagnosis and progression. Herein, we have shown that various miRNAs, like miR-155, miR?103a?3p, miR-21, and miR-130a increase the oncogenesis process, whereas some miRNAs such as miR-140-5p, miR-150, miR-375, miR-181a, miR-98, miR-125a-5p, miR-582-5p, miR-144-3p, miR-320a, miR-187 and miR-101-3p, miR-143-3p inhibit the salivary adenoid cystic carcinoma progression. Furthermore, we have found that miRNAs also target many vital genes and pathways like mitogen-activated protein kinases-snail family transcriptional repressor 2 (MAPK-Snai2), p38/JNK/ERK, forkhead box C1 protein (FOXC1), mammalian target of rapamycin (mTOR), integrin subunit beta 3 (ITGB3), epidermal growth factor receptor (EGFR)/NF-?B, programmed cell death protein 4 (PDCD4), signal transducer and activator of transcription 3 (STAT3), neuroblastoma RAS (N-RAS), phosphatidylinositol-3-kinase (PI3K)/Akt, MEK/ERK, ubiquitin-like modifier activating enzyme 2 (UBA2), tumor protein D52 (TPD52) which play a crucial role in the regulation of salivary adenoid cystic carcinoma. Therefore, we believe that knowledge from this manuscript will help us find the pathogenesis process in salivary adenoid cystic carcinoma and could also give us better biomarkers of diagnosis and prognosis of the disease. � 2022
Impact of noncoding RNAs on cancer directed immune therapies: Now then and forever
(John Wiley and Sons Inc, 2022-04-30T00:00:00) Roy, Roshan Kumar; Yadav, Rakhi; Sharma, Uttam; Wasson, Mishi Kaushal; Sharma, Ashok; Tanwar, Pranay; Jain, Aklank; Prakash, Hridayesh
Accumulating evidence demonstrates that the host genome's epigenetic modifications are essential for living organisms to adapt to extreme conditions. DNA methylation, covalent modifications of histone and interassociation of noncoding RNAs facilitate the cellular manifestation of epigenetic changes in the genome. Out of various factors involved in the epigenetic programming of the host, noncoding RNAs (ncRNAs) such as microRNA (miRNA), long noncoding RNA (lncRNA), circular RNA, snoRNA and piRNA are new generation noncoding molecules that influence a variety of cellular processes like immunity, cellular differentiation and tumor development. During tumor development, temporal changes in miRNA/lncRNA rheostat influence sterile inflammatory responses accompanied by the changes in the carcinogenic signaling in the host. At the cellular level, this is manifested by the upregulation of inflammasome and inflammatory pathways, which promotes cancer-related inflammation. Given this, we discuss the potential of lncRNAs, miRNAs, circular RNA, snoRNA and piRNA in regulating inflammation and tumor development in the host. � 2022 UICC.
LINC00324 promotes cell proliferation and metastasis of esophageal squamous cell carcinoma through sponging miR-493-5p via MAPK signaling pathway
(Elsevier Inc., 2022-12-06T00:00:00) Sharma, Uttam; Kaur Rana, Manjit; Singh, Karuna; Jain, Aklank
Long non-coding RNAs have been demonstrated to promote proliferation and metastasis via regulating the miRNA/mRNA regulatory axis in various malignancies. Based on our preliminary study, we investigated the mechanism of LINC00324 through miR-493-5p/MAPK1 in esophageal squamous cell carcinoma (ESCC) pathogenesis. Herein, we confirmed that LINC00324 is significantly upregulated in ESCC primary cells and esophageal squamous cell carcinoma cell line KYSE-70. Silencing of LINC00324 modulates cell proliferation markers, p21, p27, c-Myc, and Cyclin D1 and epithelial-to-mesenchymal transition markers, slug, snail, ZEB1, vimentin, ZO-1, and E-cadherin protein expression in ESCC. Through bioinformatics and dual luciferase reporter assays, we identified miR-493-5p as the direct target molecule of LINC00324. We further revealed that LINC00324 negatively regulates miR-493-5p expression in ESCC. Moreover, our multiple gain-and loss-of-functional experiments proved that a combination of miR-493-5p and LINC00324 significantly rescued ESCC cell proliferation and metastatic phenotypes. Mechanistically, LINC00324 promotes ESCC pathogenesis by acting as a competing endogenous RNA and sponges miR-493-5p activity thereby activating MAPK1 during ESCC progression. We believe that targeting LINC00324 /miR-493-5p/MAPK1 axis may provide new therapeutic avenues for ESCC. � 2022 Elsevier Inc.
LncRNA ZFAS1 inhibits triple-negative breast cancer by targeting STAT3
(Elsevier B.V., 2021-01-11T00:00:00) Sharma, Uttam; Barwal, Tushar Singh; Khandelwal, Akanksha; Malhotra, Akshay; Rana, Manjit Kaur; Singh Rana, Amrit Pal; Imyanitov, Evgeny N.; Vasquez, Karen M.; Jain, Aklank
Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with fewer treatment options than other types of invasive breast cancer due to the loss of the estrogen, progesterone receptors and low levels of the HER2 protein, resulting in a poor prognosis for these patients. Here, we found that the expression of the lncRNA, ZFAS1, was significantly downregulated (?3.0-fold) in blood samples of TNBC patients (n=40) compared to matched healthy controls (n=40). Functionally, silencing of ZFAS1 promoted cell proliferation and colonization of human MDA-MB-231 TNBC cells by inhibiting the expression levels of the cyclin-dependent kinase (CDK) inhibitors p21 (CDKN1A) and p27 (CDKN1B) compared to the scrambled siRNA control cells. Further, we found that downregulation of ZFAS1 led to decreased protein levels of the epithelial markers, E-cadherin, Claudin-1, and Zo-1, with increased protein levels of the mesenchymal markers, Slug and ZEB1. In addition, by utilizing the bioinformatic tools such as RAID v2.0 (RNA Interactome Database Version 2.0), AnnoLnc (Annotate human lncRNA database), and GEPIA (Gene Expression Profiling Interactive Analysis), we identified a strong negative correlation between ZFAS1 and signal transducer and activator of transcription 3 (STAT3) gene expression (R = ?0.11, p-value = 0.0002). Further, we observed that decreased ZFAS1 expression significantly (p < 0.05) increased STAT3 and phosphorylated STAT3 (at Ser727 residue) protein levels in TNBC cells. The composite data indicate that ZFAS1 may function as a tumor-suppressor lncRNA with potential as a diagnostic/prognostic marker and may offer a new target for the treatment of TNBC patients. � 2021 Elsevier B.V. and Soci�t� Fran�aise de Biochimie et Biologie Mol�culaire (SFBBM)
Macrophage Activation Syndrome and COVID 19: Impact of MAPK Driven Immune-Epigenetic Programming by SARS-Cov-2
(Frontiers Media S.A., 2021-10-01T00:00:00) Roy, Roshan Kumar; Sharma, Uttam; Wasson, Mishi Kaushal; Jain, Aklank; Hassan, Md. Imtaiyaz; Prakash, Hridayesh
[No abstract available]
Micrornas and long noncoding rnas as novel therapeutic targets in estrogen receptor-positive breast and ovarian cancers
(MDPI, 2021-04-15T00:00:00) Barwal, Tushar Singh; Sharma, Uttam; Bazala, Sonali; Singh, Ipsa; Jain, Manju; Prakash, Hridayesh; Shekhar, Shashank; Sandberg, Elise N.; Bishayee, Anupam; Jain, Aklank
Aromatase inhibitors (AIs) such as anastrozole, letrozole, and exemestane have shown to prevent metastasis and angiogenesis in estrogen receptor (ER)-positive breast and ovarian tumors. They function primarily by reducing estrogen production in ER-positive post-menopausal breast and ovarian cancer patients. Unfortunately, current AI-based therapies often have detrimental side-effects, along with acquired resistance, with increased cancer recurrence. Thus, there is an urgent need to identify novel AIs with fewer side effects and improved therapeutic efficacies. In this regard, we and others have recently suggested noncoding RNAs (ncRNAs), specifically microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), as potential molecular targets for utilization in modulating cancer hallmarks and overcoming drug resistance in several cancers, including ER-positive breast and ovarian cancer. Herein, we describe the disruptive functions of several miRNAs and lncRNAs seen in dysregulated cancer metabolism, with a focus on the gene encoding for aromatase (CYP19A1 gene) and estrogen synthesis as a novel therapeutic approach for treating ER-positive breast and ovarian cancers. Furthermore, we discuss the oncogenic and tumor-suppressive roles of several miRNAs (oncogenic miRNAs: MIR125b, MIR155, MIR221/222, MIR128, MIR2052HG, and MIR224; tumor-suppressive miRNAs: Lethal-7f, MIR27B, MIR378, and MIR98) and an oncogenic lncRNA (MIR2052HG) in aromatase-dependent cancers via transcriptional regulation of the CYP19A1 gene. Additionally, we discuss the potential effects of dysregulated miRNAs and lncRNAs on the regulation of critical oncogenic molecules, such as signal transducer, and activator of transcription 3, ?-catenin, and integrins. The overall goal of this review is to stimulate further research in this area and to facilitate the development of ncRNA-based approaches for more efficacious treatments of ER-positive breast and ovarian cancer patients, with a slight emphasis on associated treatment� delivery mechanisms. � 2021 by the authors. Licensee MDPI, Basel, Switzerland.
miR-590�5p: A double-edged sword in the oncogenesis process
(Elsevier Ltd, 2022-06-12T00:00:00) Barwal, Tushar Singh; Singh, Neha; Sharma, Uttam; Bazala, Sonali; Rani, Medha; Behera, Alisha; Kumawat, Ram Kumar; Kumar, Pawan; Uttam, Vivek; Khandelwal, Akanksha; Barwal, Jyoti; Jain, Manju; Jain, Aklank
Accumulating evidence suggests the critical role of miR-590�5p in various aspects of cellular homeostasis, including cancer. Furthermore, we and others have recently demonstrated that miRNA-590�5p acts as an oncogene in some cancers while it acts as a tumor-suppressor in others. However, the role of miR-590�5p in oncogenesis is more complex, like a double-edged sword. Thus, this systematic review introduces the concept, mechanism, and biological function of miR-590�5p to resolve this apparent paradox. We have also described the involvement of miR-590�5p in crucial cancer-hallmarks processes like proliferation, invasion, metastasis, and chemo radioresistance. Finally, we have presented the possible genes/pathways targets of miR-590�5p through bioinformatics analysis. This review may help in designing better biomarkers and therapeutic targets for cancers. � 2022
Natural flavonoids exhibit potent anticancer activity by targeting microRNAs in cancer: A signature step hinting towards clinical perfection
(Neoplasia Press, Inc., 2022-12-05T00:00:00) Tuli, Hardeep Singh; Garg, Vivek Kumar; Bhushan, Sakshi; Uttam, Vivek; Sharma, Uttam; Jain, Aklank; Sak, Katrin; Yadav, Vikas; Lorenzo, Jose M.; Dhama, Kuldeep; Behl, Tapan; Sethi, Gautam
Cancer prevalence and its rate of incidence are constantly rising since the past few decades. Owing to the toxicity of present-day antineoplastic drugs, it is imperative to explore safer and more effective molecules to combat and/or prevent this dreaded disease. Flavonoids, a class of polyphenols, have exhibited multifaceted implications against several diseases including cancer, without showing significant toxicity towards the normal cells. Shredded pieces of evidence suggest that flavonoids can enhance drug sensitivity and suppress proliferation, metastasis, and angiogenesis of cancer cells by modulating several oncogenic or oncosuppressor microRNAs (miRNAs, miRs). They play pivotal roles in regulation of various biological and pathological processes, including various cancers. In the present review, the structure, chemistry and miR targeting efficacy of quercetin, luteolin, silibinin, genistein, epigallocatechin gallate, and cyanidin against several cancer types are comprehensively discussed. miRs are considered as next-generation medicine of recent times, and their targeting by naturally occurring flavonoids in cancer cells could be deemed as a signature step. We anticipate that our compilations related to miRNA-mediated regulation of cancer cells by flavonoids might catapult the clinical investigations and affirmation in the future. � 2022
NOTCH signaling: Journey of an evolutionarily conserved pathway in driving tumor progression and its modulation as a therapeutic target
(Elsevier Ireland Ltd, 2021-06-29T00:00:00) Aggarwal, Vaishali; Tuli, Hardeep Singh; Varol, Mehmet; Tuorkey, Muobarak; Sak, Katrin; Parashar, Nidarshana Chaturvedi; Barwal, Tushar Singh; Sharma, Uttam; Iqubal, Ashif; Parashar, Gaurav; Jain, Aklank
Notch signaling, an evolutionarily conserved signaling cascade, is critical for normal biological processes of cell differentiation, development, and homeostasis. Deregulation of the Notch signaling pathway has been associated with tumor progression. Thus, Notch presents as an interesting target for a variety of cancer subtypes and its signaling mechanisms have been actively explored from the therapeutic viewpoint. However, besides acting as an oncogene, Notch pathway can possess also tumor suppressive functions, being implicated in inhibition of cancer development. Given such interesting dual and dynamic role of Notch, in this review, we discuss how the evolutionarily conserved Notch signaling pathway drives hallmarks of tumor progression and how it could be targeted for a promising treatment and management of cancer. In addition, the up-to-date information on the inhibitors currently under clinical trials for Notch targets is presented along with how NOTCH inhibitors can be used in conjunction with established chemotherapy/radiotherapy regimes. � 2021 Elsevier B.V.
A Pleiotropic Role of Long Non-Coding RNAs in the Modulation of Wnt/?-Catenin and PI3K/Akt/mTOR Signaling Pathways in Esophageal Squamous Cell Carcinoma: Implication in Chemotherapeutic Drug Response
(MDPI, 2022-03-28T00:00:00) Sharma, Uttam; Murmu, Masang; Barwal, Tushar Singh; Tuli, Hardeep Singh; Jain, Manju; Prakash, Hridayesh; Kaceli, Tea; Jain, Aklank; Bishayee, Anupam
Despite the availability of modern techniques for the treatment of esophageal squamous cell carcinoma (ESCC), tumor recurrence and metastasis are significant challenges in clinical management. Thus, ESCC possesses a poor prognosis and low five-year overall survival rate. Notably, the origin and recurrence of the cancer phenotype are under the control of complex cancer-related signaling pathways. In this review, we provide comprehensive knowledge about long non-coding RNAs (lncRNAs) related to Wnt/?-catenin and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in ESCC and its implications in hindering the efficacy of chemotherapeutic drugs. We observed that a pool of lncRNAs, such as HERES, TUG1, and UCA1, associated with ESCC, directly or indirectly targets various molecules of the Wnt/?-catenin pathway and facilitates the manifestation of multiple cancer phenotypes, including proliferation, metastasis, relapse, and resistance to anticancer treatment. Additionally, several lncRNAs, such as HCP5 and PTCSC1, modulate PI3K/Akt/mTOR pathways during the ESCC pathogenesis. Furthermore, a few lncRNAs, such as AFAP1-AS1 and LINC01014, block the efficiency of chemotherapeutic drugs, including cisplatin, 5-fluorouracil, paclitaxel, and gefitinib, used for ESCC treatment. Therefore, this review may help in designing a better therapeutic strategy for ESCC patients. � 2022 by the authors. Licensee MDPI, Basel, Switzerland.