Biochemistry And Microbial Sciences - Research Publications

Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/27

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Author: search.filters.author.Sharma, Uttam

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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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    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, Aklank
    As 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.
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    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.
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    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, Aklank
    Cancer 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.
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    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.