• NILADRI GANGULY

      Articles written in Journal of Biosciences

    • Human papillomavirus E6 and E7 oncoproteins as risk factors for tumorigenesis

      Niladri Ganguly Suraj P Parihar

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      Human papillomavirus (HPV) is small, double-stranded DNA virus that infects mucosal and cutaneous epithelial tissue. HPV is sexually transmitted and the viral DNA replicates extrachromosomally. The virus is non-enveloped and has an icosahedral capsid. There are approximately 118 types of HPV, which are characterized as high-risk or low-risk types. High-risk HPVs cause malignant transformation while the low-risk ones cause benign warts and lesions. The expression of E6 and E7 is normally controlled during the normal viral life cycle when viral DNA replicates extrachromosomally. HPV E6 and E7 oncoproteins are overexpressed when the viral genome integrates into the host DNA. Deregulated overexpression of E6 and E7 oncoproteins can cause several changes in cellular pathways and functions leading to malignant transformation of cells and tumorigenesis. In this review, we focus on several cellular mechanisms and pathways that are altered in the presence of E6 and E7, the target proteins of E6 and E7 inside the host cell and how they contribute to the development of the transformed phenotype..

    • CRISPR-mediated knockdown of miR-214 modulates cell fate in response to anti-cancer drugs in HPV-negative and HPVpositive cervical cancer cells

      PRAKRITI SEN SAYAM GHOSAL RUDRANIL HAZRA RIMJHIM MOHANTY SOLOMON AREGA BIKASH SAHU NILADRI GANGULY

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      Cervical cancer is the fourth most common cause of mortality in women worldwide. In this study weinvestigated the effect of a tumour suppressor microRNA miR-214 in modulating the cell death againstchemotherapeutic drugs like Doxorubicin, Cisplatin and Paclitaxel. CRISPR-facilitated knockdown andplasmid-based overexpression of miR-214 was performed in cervical cancer cell lines HeLa, C33A and CaSki.It was observed that knocking out miR-214 resulted in reduced apoptosis and cell migration upon drugtreatments; while overexpression of miR-214 resulted in marginal increase in apoptosis and cell migrationwhen treated with drugs. However, miR-214 had very little effect on production of reactive oxygen species.Our results also indicate that Doxorubicin was least effective and Paclitaxel most effective in inducing celldeath. A combination of miR-214 overexpression and Paclitaxel treatment was found to be most effective ininducing cell death in cervical cancer cells. Analysis of cell cycle phases followed by apoptotic markers alsoshowed that miR-214 overexpression along with Paclitaxel treatment caused an increase in PARP and declineof PI-3 kinase/Akt levels. Therefore, miR-214 levels determine the fate of the cancer cell duringchemotherapeutic treatment.

    • Differential transcriptome analysis in HPV-positive and HPV-negative cervical cancer cells through CRISPR knockout of miR-214

      PRAKRITI SEN POOJA GANGULY KIRTI K KULKARNI ROLI BUDHWAR NILADRI GANGULY

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      In this study we have investigated the effects of a tumour suppressor microRNA, miR-214, on gene expressionin HPV-positive (CaSki) and HPV-negative cervical cancer cells (C33A) by RNA sequencing using nextgeneration sequencing. The HPV-positive and HPV-negative cervical cancer cells were either miR-214-knocked-out or miR-214-overexpressed. Gene expression analysis showed that a total of 904 genes wereupregulated and 365 genes were downregulated between HPV-positive and HPV-negative cervical cancer cellswith a fold change of ±2. Furthermore, 11 differentially expressed and relevant genes (TNFAIP3, RAB25,MET, CYP1B1, NDRG1, CD24, LOXL2, CD44, PMS2, LATS1 and MDM1) which showed a fold change of ±5were selected to confirm by real-time PCR. This study represents the first report of miR-214 on global geneexpression in the context of HPV.

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