School Of Basic And Applied Sciences

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Author: search.filters.author.Jain, AklankSubject: search.filters.subject.LncRNA

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    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.
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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.