Biology subjects

Gopal, C.

Publications and source records attributed to Gopal, C..

3 recordsLinked to original sources

bioRxiv2025

miR-631 targets the oncogene RAB11A: implications for oral squamous cell carcinoma pathogenesis and therapeutics

Despite technological advancements, the five-year survival rate for oral squamous cell carcinoma (OSCC) remains dismally low. To develop more effective therapies, we intended to identify the potential therapeutic tumor suppressor microRNAs in OSCC. Previously, a microRNA microarray analysis of 5-Azacytidine treated SCC131 cells had identified 50 upregulated miRs. Of these, miR-631 that had no previously known roles in OSCC was selected for further analysis in the present study. We show that miR-631 binds directly to the oncogene RAB11A and reduces its transcript and protein levels. The upregulation of miR-631 occurs due to its gene promoter demethylation after 5-Azacytidine treatment. We demonstrate that miR-631 reduces proliferation and anchorage-independent growth of OSCC cells in soft agar and promotes apoptosis, in part, via targeting RAB11A. An inverse relationship between miR-631 and RAB11A levels observed across multiple cancer cell lines and in 58.33% of OSCC patient samples highlights the biological significance of their interaction. Further, miR-631 and RAB11A interaction reduces the Wnt signaling in OSCC. Additionally, the nude mice OSCC xenograft study proves the tumor suppressive nature of miR-631. Based on our results, we propose that miR-631 holds promise as a potential therapeutic agent for treating OSCC.

cancer biology↗

bioRxiv2023

Intronic miR-6741-3p is involved in oral squamous cell carcinoma pathogenesis by targeting the oncogene SRSF3

Epigenetic silencing through methylation is one of the major mechanisms for downregulation of tumor suppressor miRNAs in various malignancies. The aim of this study was to identify novel tumor suppressor miRNAs which are silenced by DNA hypermethylation and investigate the role of at least one of these in oral squamous cell carcinoma (OSCC) pathogenesis. We treated cells from an OSCC cell line SCC131 with 5-Azacytidine, a DNA methyltransferase inhibitor, to reactivate tumor suppressor miRNA genes silenced/downregulated due to DNA methylation. At 5-day post-treatment, total RNA was isolated from the 5-Azacytidine and vehicle control-treated cells. The expression of 2,459 mature miRNAs was analysed between 5-Azacytidine and control-treated OSCC cells by the microRNA microarray analysis. Of the 50 miRNAs which were found to be upregulated following 5-Azacytidine treatment, we decided to work with miR-6741-3p in details for further analysis, as it showed a mean fold expression of >4.0. The results of qRT-PCR, Western blotting, and dual-luciferase reporter assay indicated that miR-6741-3p directly targets the oncogene SRSF3 at the translational level only. The tumor-suppressive role of miR-6741-3p was established by various in vitro and in vivo assays. Our results revealed that miR-6741-3p plays a tumor-suppressive role in OSCC pathogenesis, in part, by directly regulating SRSF3. Based on our observations, we propose that miR-6741-3p may serve as a potential biological target in tumor diagnostics, prognostic evaluation, and treatment of OSCC and perhaps other malignancies.

cancer biology↗

bioRxiv2023

Cytotoxic rhamnolipid micelles drive acute virulence in Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic human pathogen that has developed multi- or even pan-drug resistance towards most frontline and last resort antibiotics, leading to increasing infections and deaths among hospitalized patients, especially those with compromised immune systems. Further complicating treatment, P. aeruginosa produces numerous virulence factors that contribute to host tissue damage and immune evasion, promoting bacterial colonization and pathogenesis. In this study, we demonstrate the importance of rhamnolipid production in host-pathogen interactions. Secreted rhamnolipids form micelles that exhibited highly acute toxicity towards murine macrophages, rupturing the plasma membrane and causing organellar membrane damage within minutes of exposure. While rhamnolipid micelles (RMs) were particularly toxic to macrophages, they also caused membrane damage in human lung epithelial cells, red blood cells, Gram-positive bacteria, and even non-cellular models like giant plasma membrane vesicles. Most importantly, rhamnolipid production strongly correlated to P. aeruginosa virulence against murine macrophages in various panels of clinical isolates. Altogether, our findings suggest that rhamnolipid micelles are highly cytotoxic virulence factors that drive acute cellular damage and immune evasion during P. aeruginosa infections.

microbiology↗