<p>MicroRNA-218 regulates the chemo-sensitivity of cervical cancer cells through targeting survivin</p>

Abstract

Background: Cervical cancer is one of the most lethal malignancies among women in the world. Every year about 311,365 women die because of cervical cancer. Chemo-resistance is the main reason of the lethal malignancies, and the mechanism of chemo-resistance in cervical cancer still remains largely elusive. Purpose: Previous studies reported that microRNAs played important biological roles in the chemo-resistance in many types of cancers, in the present study we tried to investigate the biological roles of microRNA-218 in chemo-resistance in cervical cancer cells. Results: Real-time PCR results indicated microRNA-218 was downregulated in cisplatin-resistant HeLa/DDP and SiHa/DDP cells compared with the mock HeLa and SiHa cells. CCK-8 assay results showed upregulation of microRNA-218 enhanced the cisplatin sensitivity of cervical cancer cells; while downregulation of microRNA-218 decreased the cisplatin sensitivity of cervical cancer cells. Dual-luciferase assay indicated survivin was a direct target of microRNA-218. Western blotting and PCR results indicated the expression of survivin in HeLa/DDP and SiHa/DDP cells was significantly increased compared with HeLa and SiHa cells. Further study indicated induction of microRNA-218 decreased the expression of survivin while inhibition of microRNA-218 increased the expression of survivin in cervical cancer cells. Cell apoptosis results indicated induction of microRNA-218 induced the cell apoptosis in cervical cancer cells. Conclusion: Our data revealed microRNA-218 enhanced the cisplatin sensitivity in cervical cancer cells through regulation of cell growth and cell apoptosis, which could potentially benefit to the cervical cancer treatment in the future.

Licochalcone A inhibits EGFR signalling and translationally suppresses survivin expression in human cancer cells

“…[47][48][49] Additionally, targeting survivin enhanced tumour chemo-and radio-sensitivity. [50][51][52] Our data demonstrated that licochalcone A translationally regulates survivin expression, but exhibits no significant effect on mRNA level and protein stability. Importantly, licochalcone A-mediated survivin down-regulation is partly dependent on the suppression of EGFR downstream Akt and ERK1/2 signallings, which is consistent with the previous report that reduces survivin protein by brexpiprazole overcomes EGFR TKI resistance in lung and pancreatic cancer.…”

“…Indeed suppression of transactivation of survivin through direct binding to its promoter, the small molecule inhibitors YM‐155 and terameprocol (EM‐1421) decreased survivin protein and induced apoptosis in human cancer cells 47‐49 . Additionally, targeting survivin enhanced tumour chemo‐ and radio‐sensitivity 50‐52 . Our data demonstrated that licochalcone A translationally regulates survivin expression, but exhibits no significant effect on mRNA level and protein stability.…”

The Role of microRNAs in the Cisplatin- and Radio-Resistance of Cervical Cancer

“…A growing body of evidence suggested miR-218 as significantly downregulated in human cancer tissues compared to the adjacent non-cancerous tissues [ 54 , 55 ], including cervical cancer [ 56 ], where it plays a role as a tumor-suppressor miRNA. MiR-218 was found to be significantly downregulated in cisplatin-resistant HeLa and SiHa cells compared to parental controls reaching a 60% decrease in both cell lines [ 40 ] ( Table 1 ). Survivin, one of the well-known inhibitors of apoptosis, was identified as a miR-218 target, thus the suppression of this miR in HeLa and SiHa cells ensures cell survival through a survivin-dependent mechanism [ 40 ].…”

Recent advances in the contribution of noncoding RNAs to cisplatin resistance in cervical cancer

“…Ectopic expression of miR-214 reduces the expression of the protective Bcl2-like 2 protein and increases the expression of the pro-apoptotic proteins Bax, caspase-9, caspase-8, and caspase-3 in CC cells, leading to enhanced apoptosis and CDDP sensitivity (Wang et al, 2013). Similarly, miRNA-218 can reduce the expression of survivin both in mRNA and protein level, a member of the inhibitor of apoptosis protein family, thereby increasing CDDP sensitivity in CC cells (Yu et al, 2019).…”