MicroRNA-7-5p Promotes Cisplatin Resistance of Cervical Cancer Cells and Modulation of Cellular Energy Homeostasis by Regulating the Expression of the PARP-1 and BCL2 Genes

Abstract

BackgroundResistance to cisplatin results in recurrence or relapse of cervical cancer in women. An understanding of the mechanisms of cisplatin resistance will be important to improve the efficacy of cisplatin treatment. The aim of this study was to investigate the role of microRNA-7-5p (mir-7-5p) in cisplatin-resistant cervical cancer cells in vitro.Material/MethodsThe expression levels of miR-7-5p were detected in cisplatin-resistant cervical cancer cells, HeLa, and SiHa cells (HPV16-positive), and in clinical tissue samples, using miR-7-5p inhibition and a luciferase reporter assay. Fifteen paired cervical cancer tissue samples and adjacent normal cervical tissues were obtained from 15 patients who underwent surgery for cervical cancer. Western blot and flow cytometry were used to investigate cell apoptosis. The expression of mir-7-5p was detected by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR).ResultsThe level of miR-7-5p was increased in cisplatin-resistant HeLa and SiHa cervical cancer cells. Increased expression of miR-7-5p inhibited DNA repair by modulating the expression of poly (ADP-ribose) polymerase 1 (PARP-1), reducing energy consumption, and promoting autophagy via suppression of the expression of Bcl-2. These findings supported that increasing energy generation and reducing energy consumption, resulted in miR-7-5p maintaining energy homeostasis during cisplatin treatment.ConclusionsThe findings of this study showed that there was a protective role of miR-7-5p in cervical cancer cells treated with cisplatin and that miR-7-5p expression maintained energy homeostasis in cisplatin-resistant cervical cancer cells. However, miR-7-5p reduced energy consumption via inhibiting PARP-1 expression, and miR-7-5p increased energy generation by suppressing the expression of Bcl-2.

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

“…These results indicated a possible link between miRNAs and CDDP sensitivity through the regulation of mismatch repair. Poly (ADP-ribose) polymerase 1 (PARP-1) is an important regulator of DNA repair and is negatively regulated by miR-7-5p, suggesting another mechanism by which miRNAs could contribute to CDDP resistance (Yang et al, 2018). Indeed, the PARP inhibitor olaparib has been shown to enhance the sensitivity of CC cells to CDDP (Prasad et al, 2017), substantiating the potential for miRNAs to provide new therapeutic targets.…”

“…biomarkers to predict chemosensitivity and thus improve treatment regimens in this patient population. The ncRNAs known to be differentially expressed in drug-resistant CC compared with normal tissues include miR-7-5p (Yang et al, 2018), miR-21 ( Feng et al, 2017), miR-130a (Feng et al, 2018), miR-181a (Chen et al, 2014), which are upregulated, and lncRNA CACS2, which is downregulated in CDDP-resistant CC (Feng et al, 2017). Analysis of the expression of ncRNAs in CC patients in combination with other molecular markers may predict the patient's response and thus identify those who would most benefit from CDDP.…”

“…Treatment of CDDP-resistant CC cells with a miR-25-3p mimic significantly sensitized them to growth inhibition by CDDP (Song & Li, 2017). Conversely, blockade of miR-7-5p with antisense oligonucleotide -miR-7-5p increased the apoptosis rate of CDDP-resistant CC cells (Yang et al, 2018). However, there have been no clinical trials or clinically relevant animal trials of these agents for CC to date.…”

<p>NEAT1 Knockdown Suppresses the Cisplatin Resistance in Ovarian Cancer by Regulating miR-770-5p/PARP1 Axis</p>

“…16,17 Poly adenosine diphosphate-ribose polymerase 1 (PARP1) is a crucial target of miR-7-5p, which is involved in DNA repair and contributes to chemoresistance. 18,19 Moreover, previous studies suggest that PARP1 contributes to the development and cisplatin resistance in ovarian cancer, 20,21 and miR-216b could promote cisplatin sensitivity in ovarian cancer via decreasing PARP1. 22 However, there is no evidence supporting the interaction between NEAT1 and miR-770-5p or PARP1 at the moment.…”

LncRNA ZFAS1 contributed to irradiation resistance in nasopharyngeal carcinoma by inhibiting hsa-miR-7-5p/ENO2

“…Only that Kazuo's team reported in 2019 that miR-7-5p was up-regulated in clinically relevant resistance HeLa (cervical cancer cell line) and SAS (oral squamous cell carcinoma) cell lines [28]. In addition, controversial roles of miR-7-5p in chemo-drug resistance have been reported in human hepatocellular carcinoma [29], cervical cancer [30], breast cancer [31], and small cell lung cancer [32]. Whether in nasopharyngeal miR-7-5p promotes radio resistance remains undiscovered.…”