Background Concurrent chemoradiotherapy is the treatment for advanced cervical cancer (CC), and cisplatin (CDDP) is currently one of the main drugs in clinical chemotherapy. However, the development of CDDP resistance severely limits its clinical application, making it essential to investigate the mechanisms underlying CDDP resistance for the treatment of CC.
Objective To explore the role of POT1-AS1, a long non-coding RNA, in CDDP resistance in CC.
Methods Based on the TCGA database, we investigated the expression of POT1-AS1 in CC tissues and normal tissues, and analyzed the relationship between POT1-AS1 expression levels and prognosis. CCK-8 assay was used to compare the viability of resistant cell lines after CDDP treatment with that of parental cell lines and siPOT1-AS1 and siNC groups, and to determine the corresponding half maximal inhibitory concentration (IC50). QPCR was used to examine the expression of POT1-AS1 in resistant cell lines and corresponding parental cell lines as well as the correlation between POT1-AS1 expression and the duration time of CDDP treatment. Colony formation assays was used to examine the effect of POT1-AS1 on the proliferation of CDDP-resistant cells. PI/DAPI double staining fluorescence was used to assess the correlation between POT1-AS1 and CDDP induced cell death.
Results POT1-AS1 was highly expressed in CC tumor tissues and associated with poor prognosis. The cell viability and IC50 values of the resistant cell lines were significantly higher than those of the parental cell lines (P＜0.001), and they were significantly lower in the POT1-AS1 silenced group than those in the negative control group (P＜0.001), with statistically significant differences. The expression of POT1-AS1 in resistant cell lines was significantly higher than that in parental cell lines (P＜0.001), and it increased with prolonged CDDP administration. POT1-AS1 silencing could significantly inhibit the proliferation of drug-resistant cells (P < 0.01). The resistant cell death rate of CC increased significantly in the POT1-AS1 silenced group compared with the negative control group (P＜0.01), especially after CDDP treatment (P＜0.01).
Conclusion POT1-AS1 is closely associated with CDDP resistance of CC and plays a cancer promoting role by inhibiting CDDP mediated cell death.
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