School Of Basic And Applied Sciences

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    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)
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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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    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.