MicroRNA let-7g acts as tumor suppressor and predictive biomarker for chemoresistance in human epithelial ovarian cancer

Abstract

Remarkable deregulation of microRNAs has been demonstrated in epithelial ovarian cancer (EOC). In particular, some of the let-7 miRNA family members have been proposed as tumor suppressors. Here, we explored the functional roles of let-7g in EOC. The ectopic overexpression of let-7g in OVCAR3 and HEY-A8 EOC cells induced i) a down-regulation of c-Myc and cyclin-D2 thus promoting cell cycle arrest, ii) a reduction of Vimentin, Snail and Slug thus counteracting the progression of epithelial to mesenchymal transition, iii) a chemosensitization to cis -platinum treatment. Next, analysis of human EOC tissues revealed that let-7g expression was significantly reduced in tumor tissue specimens of patients with EOC compared to their non-tumor counterparts ( p = 0.0002). Notably, low let-7g tissue levels were significantly associated with acquired chemoresistance of patients with late-stage of EOC (n = 17, p = 0.03194). This finding was further validated in the serum samples collected from the same cohort of patients (n = 17, p = 0.003). To conclude, we demonstrate that let-7g acts as tumor suppressor and might be used to disable EOC tumor progression and chemoresistance to cis -platinum-based chemotherapy. Furthermore, we propose that decreased expression of let-7g could serve as a tissue and serum biomarker able to predict the chemo-resistant features of EOC patients.

Epigenetic Biomarkers in the Management of Ovarian Cancer: Current Prospectives

“…10 miRs which were identified using genome wide MicroRNA expression profiling were capable to discriminate malignant tissue samples from normal with a sensitivity of 97% and specificity of 92% (Wang et al, 2014). Biamonte et al have reported tumor suppressive role of miR-let-7g and significant association of its reduced expression in both tissue as well as serum with chemoresistance in advanced stage EOC patient which reflects its potential as a predictive biomarker to monitor response to chemotherapy (Biamonte et al, 2019). Kobayashi et al have shown significant overexpression of serum miR-1290 in advance stage HGSOC in comparison to early stage.…”

FtH-Mediated ROS Dysregulation Promotes CXCL12/CXCR4 Axis Activation and EMT-Like Trans-Differentiation in Erythroleukemia K562 Cells

“…K562 cells were cultured on cover slip coated with fibronectin for 24 h. Samples preparation was performed as reported in Biamonte et al (39). Thereafter, these cover slips were incubated for 1 h with primary antibodies anti-Vimentin (clone V9, ready to use, Dako) and 1 h with secondary antibody FITC-conjugated anti-mouse diluted in blocking buffer.…”

Mikrorna – Molekul Versatil Dalam Kanser Tiroid

“…Ekspresi rendah let-7 dilaporkan berkaitrapat dengan jangka hayat yang pendek di kalangan pesakit kanser paru-paru (Takamizawa et al, 2004). Beberapa kajian juga melaporkan bahawa aktiviti penindas tumor let-7 melingkungi pelbagai jenis kanser termasuklah gastrik (Ishiguro et al, 2014), kolon (Mizuno et al, 2018) dan ovari (Biamonte et al, 2019).…”