Involvement of miR-619-5p in resistance to cisplatin by regulating ATXN3 in oral squamous cell carcinoma

Abstract

MicroRNAs are major post-transcriptional regulators responsible for the development of human cancers, including OSCC. The specific role of miR-619-5p in OSCC, however, is rarely reported. Cisplatin is one of the mostly applied chemotherapy drugs of OSCC. Nevertheless, drug resistance of cisplatin following the initial chemotherapy largely restricts its clinical benefits, and the mechanism of cisplatin resistance is unclear. This study intends to explore the biological function of miR-619-5p in the development of cisplatin resistance in OSCC cell lines and a xenograft model, as well as the potential molecular mechanism. Our results showed that miR-619-5p was down-regulated in OSCC samples and cisplatin-resistant OSCC cells. Ectopically expressed miR-619-5p inhibited proliferative, migratory and invasive abilities of OSCC cisplatin-resistant cells. The putative target gene ATXN3 was predicted by bioinformatic analysis and confirmed by dual-luciferase reporter assay. Importantly, ATXN3 was responsible for the regulatory effects of miR-619-5p on biological behaviors of cisplatin-resistant OSCC cells. Moreover, miR-619-5p mimics and ATXN3-siRNA significantly enhanced ATXN3 knockdown in both HN6/CDDPR and CAL27/CDDPR cells and inhibited expression of PI3K and AKT. In vivo evidences demonstrated that intratumoral injection of miR-619-5p agomir remarkably slowed down the growth of OSCC in xenograft mice. Collectively, microRNA-619-5p was the vital regulator for regulating cisplatin resistance of OSCC, which may be served as a potential therapeutic target.

MJDs family members: Potential prognostic targets and immune-associated biomarkers in hepatocellular carcinoma

“…The miR-619-5p/ATXN3 axis provided the potential molecular mechanism of OSCC, especially for promoting drug resistance of cisplatin of OSCC. And ATXN3 may be a putative therapeutic target for OSCC patients (Song et al, 2021). In addition, ATXN3 knockdown can inhibit cell growth.…”

“…Recent studies reported that oral squamous cell carcinoma (OSCC) (Song et al, 2021), testicular cancer (TC) (Shi et al, 2018), colon cancer (Li et al, 2019), breast cancer (BC) (Zou et al, 2019), anaplastic thyroid carcinoma (ATC) (Zhuang et al, 2021), neuroblastoma (NB) (Gong et al, 2021), non-small cell lung cancer (NSCLC) (Sacco et al, 2014), and breast cancer stem cells (Zhu et al, 2019)were closely related to ATXN3. For example, for oral squamous cell carcinoma, it had been studied that down-regulated miR-619-5p promoted the proliferation, migration, and invasion abilities by enhancing ATXN3 expression in OSCC cisplatin-resistant cells.…”

C1R, CCL2, and TNFRSF1A Genes in Coronavirus Disease-COVID-19 Pathway Serve as Novel Molecular Biomarkers of GBM Prognosis and Immune Infiltration

“…Mucosal-associated invariant T (MAIT) cells and γδ T cells released inflammatory cytokines to respond to invasion [ 10 ]. Early response immune effector cells, including CTL and NK cells, were activated to fight the virus [ 11 ]. A number of studies have shown that the sign of COVID-19 was the cytokine storm with elevated levels of interleukin-6 (IL-6), IL-1 β , complement C1r (C1R), tumor necrosis factor-alpha (TNF- α ), chemokine (C-C-motif) ligand 2 (CCL2), and granulocyte-macrophage colony-stimulating factor (GM-CSF) [ 12 ].…”

MicroRNAs as the pivotal regulators of cisplatin resistance in head and neck cancers

“…It has been found that miR-619-5p reduced OSCC cells migration via PI3K/AKT pathway. MiR-619-5p increased CDDP sensitivity in OSCC cells by ATXN3 targeting [ 190 ].…”