Biochemistry And Microbial Sciences - Research Publications
Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/27
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Item 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, AklankAccumulating 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. � 2022Item STAT signaling as a target for intervention: from cancer inflammation and angiogenesis to non-coding RNAs modulation(Springer Science and Business Media B.V., 2022-04-26T00:00:00) Tuli, Hardeep Singh; Sak, Katrin; Iqubal, Ashif; Garg, Vivek Kumar; Varol, Mehmet; Sharma, Uttam; Chauhan, Abhishek; Yerer, Mukerrem Betul; Dhama, Kuldeep; Jain, Manju; Jain, AklankAs a landmark, scientific investigation in cytokine signaling and interferon-related anti-viral activity, signal transducer and activator of transcription (STAT) family of proteins was first discovered in the 1990s. Today, we know that the STAT family consists of several transcription factors which regulate various molecular and cellular processes, including proliferation, angiogenesis, and differentiation in human carcinoma. STAT family members play an active role in transducing signals from cell membrane to nucleus through intracellular signaling and thus activating gene transcription. Additionally, they are also associated with the development and progression of human cancer by facilitating inflammation, cell survival, and resistance to therapeutic responses. Accumulating evidence suggests that not all STAT proteins are associated with the progression of human malignancy; however, STAT3/5 are constitutively activated in various cancers, including multiple myeloma, lymphoma, breast cancer, prostate hepatocellular carcinoma, and non-small cell lung cancer. The present review highlights how STAT-associated events are implicated in cancer inflammation, angiogenesis and non-coding RNA (ncRNA) modulation to highlight potential intervention into carcinogenesis-related cellular processes. � 2022, The Author(s), under exclusive licence to Springer Nature B.V.Item 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, AnupamDespite 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.Item Potential clinical application of lncRNAs in pediatric cancer(Elsevier, 2022-01-28T00:00:00) Chhabra, Ravindresh; Neyol, Priyasha; Bazala, Sonali; Singh, Ipsa; Murmu, Masang; Sharma, Uttam; Barwal, Tushar Singh; Jain, AklankCancer is the leading cause of death by disease in children globally. The childhood cancer burden is more than 80% in the low- and middle-income countries, including India. In contrast to cancer in adults, the number of children diagnosed with cancer is far less but the children who survive cancer are more likely to face the negative consequences of chemotherapy and radiotherapy in their lifetime. The common childhood cancers include leukemia, neuroblastoma, osteosarcoma, retinoblastoma, rhabdomyosarcoma, and Wilms tumor. Long noncoding RNAs (lncRNAs) are a pervasive subset of noncoding RNAs. The high throughput sequencing studies estimate the number of lncRNAs to be more than 100, 000 but hardly 1% of them have been functionally characterized. The lncRNAs have a tissue-specific expression and a majority of them are functionally dysregulated in numerous physiological and pathological conditions, including cancer, thereby making them attractive therapeutic targets. Recently, their role has also been described in pediatric cancers. This chapter summarizes the current knowledge about dysregulated lncRNAs, their potential as biomarker and therapeutic targets, and their underlying molecular mechanisms in pediatric cancer. � 2022 Elsevier Inc. All rights reserved.Item 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, AklankAromatase 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.Item Low dose radiation primed iNOS + M1macrophages modulate angiogenic programming of tumor derived endothelium.(PLOS, 2018) Nadella, Vinod; Singh Sandhya; Jain, Aklank; Jain, Manju; Vasquez, Karen M.; Sharma, Ashok; Tanwar, Pranay; Rath, Goura Kishore; Prakash Hridayesh.Solid tumors are covered by stroma, which is hypoxic in nature and composed of various non‐malignant components such as endothelial cells, fibroblasts, and pericytes that support tumor growth. Tumor stroma represents a mechanical barrier for tumor infiltration of CD8+ effector T cells in particular. In this context, our previous studies have demonstrated the therapeutic impact of Low‐Dose Radiation (LDR)‐primed and M1‐retuned (iNOS+) peritumoral macrophages that produce inducible nitric oxide, have immunological roles on tumor infiltration of effector T cells, cancer‐related inflammation, and subsequent tumor immune rejection in a mouse model of pancreatic cancer. These findings suggested a possible modification of tumor endothelium by LDR‐primed macrophages. In line with these observations, here we demonstrate the influence of LDR in down‐modulating HIF‐1 in irradiated tumors in the course of polarization of irradiated tumor‐associated macrophages toward an M1 phenotype. Furthermore, we demonstrate that M1 macrophages which are primed by LDR can directly influence angiogenic responses in eNOS+ endothelial cells which produce nitric oxide having both vascular and physiological roles. Furthermore, we demonstrate that naïve macrophages, upon differentiating to an M1 phenotype either by Th1 stimuli or LDR, potentially modify sphingosine‐1‐phosphate/VEGF‐induced angiogenic signaling in tumor‐derived endothelial cells with tumorigenic potential, thus indicating the significance of iNOS+ macrophages in modulating signaling in eNOS+ tumor‐derived endothelium. Our study suggests that iNOS+ macrophages can activate tumor endothelium which may contribute to cancer‐directed immunotherapy in particular.Item Atypical leishmaniasis: A global perspective with emphasis on the Indian subcontinent(Public Library of Science, 2018) Thakur L.; Singh K.K.; Shanker V.; Negi A.; Jain, Aklank; Matlashewski G.; Jain, ManjuBackground: Among the neglected tropical diseases, leishmaniasis continues to be prevalent in many tropical and subtropical countries despite international, national, and local efforts towards its control and elimination over the last decade. This warrants a critical evaluation of such factors as under-reporting, asymptomatic infections, post kala azar dermal leishmaniasis (PKDL) cases, and drug resistance. In this review, we highlight lesser-understood atypical presentations of the disease involving atypical parasite strains against a background of classical leishmaniasis with a focus on the Indian subcontinent. Methods and findings: A literature review based on endemic areas, the nature of disease manifestation, and underlying causative parasite was performed with data collected from WHO reports for each country. Searches on PubMed included the term 'leishmaniasis' and ' eishmaniasis epidemiology' alone and in combination with each of the endemic countries, Leishmania species, cutaneous, visceral, endemic, non-endemic, typical, classical, atypical, and unusual with no date limit and published in English up to September 2017. Our findings portray a scenario with a wider distribution of the disease in new endemic foci, with new discoveries of parasite-driven atypical disease manifestations in different regions of the world. Unlike the classical picture, some Leishmania species are associated with more than one disease presentation, e.g., the L. donovani complex, generally associated with the visceral form, is now also associated with a cutaneous disease presentation, while L. tropica species complex, known to cause cutaneous disease, can cause viscerotropic disease. This phenomenon points towards the discovery of novel parasite variants as etiologic agents of atypical disease manifestations and represents an excellent opportunity to identify and study genes that control disease virulence and tropism. Conclusions: The increased recognition of atypical leishmaniasis as an outcome of parasite variants has major implications for leishmaniasis control and elimination. Identifying molecular correlates of parasite isolates from distinct regions associated with different disease phenotypes is required to understand the current epidemiology of leishmaniasis in regions with atypical disease.-2018 Thakur et al. http://creativecommons.org/licenses/by/4.0/.