Browsing by Author "Uttam, Vivek"

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    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.
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    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
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    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
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    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
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    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
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    Role of Hedgehog and Hippo signaling pathways in cancer: A special focus on non-coding RNAs
    (Academic Press, 2022-10-28T00:00:00) Sharma, Uttam; Tuli, Hardeep Singh; Uttam, Vivek; Choudhary, Renuka; Sharma, Bunty; Sharma, Ujjawal; Prakash, Hridayesh; Jain, Aklank
    Despite advanced clinical and translational oncology research, mortality rates are still increasing worldwide. Recently, a class of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have been well investigated in regulating biological, molecular, and cellular signaling pathways. This review article provided the current research progress on how miRNAs, lncRNAs, and circRNAs regulate Hedgehog (Hh) and Hippo signaling pathways in various cancers. These ncRNAs target both pathways' key downstream molecules and may be used for targeted cancer treatment. Moreover, Hh and Hippo signaling pathways crosstalked with each other through Gli1 of Hh pathways and YAP1/TEAD molecules of Hippo pathways during cancer progression. Additionally, Hh and Hippo signaling pathways regulate resistance against the chemo, radio, and immune therapies for several types of cancer via inducing GLI and YAP/TAZ proteins level. Therefore, to improve the treatment regime, we presented the role of various prominent phytochemicals such as curcumin, resveratrol, genistein, quercetin, paclitaxel, and silibinin in regulating lncRNAs, miRNAs, circRNA through Hedgehog and Hippo signaling pathways� constituents in cancers. We believe that knowledge obtained from this review may help make new drugs for cancer treatment in the future. � 2022 Elsevier Ltd