Growth arrest‐specific 5 attenuates cisplatin‐induced apoptosis in cervical cancer by regulating STAT3 signaling via miR‐21

Abstract

Cervical cancer is the most common cause of female cancer‐related mortality worldwide. Decreased expression of long noncoding RNA growth arrest‐specific 5 (GAS5) is found in human cervical cancer tissues and associated with poor prognosis. However, the studies on associations between GAS5 level and malignant phenotypes, as well as sensitivity to chemotherapeutic drug in cervical cancer cells are limited. In this study, overexpression of GAS5 in cervical cancer cells resulted in prohibited cell proliferation and colony formation, which were promoted by siGAS5. Enhanced GAS5 increased cell percentage in the G0/G1 phase and decreased cells percentage in the S phase, whereas reduced expression did not. The malignant behaviors of cervical cancer cells, manifested by cell migration and invasion, could be weakened by the GAS5 overexpression and enhanced by siGAS5. Furthermore, in cisplatin‐induced cell, overexpression of GAS5 reduced cells viability and enhanced apoptosis, whereas in cells transfected with siGAS5, apoptosis eliminated. We have reported the upregulation of microRNA‐21 (miR‐21) and its oncogenetic roles in cervical cancer previously. In this study, we found the negative relationship between the GAS5 and miR‐21. Moreover, the decrease of miR‐21 associated proteins phosphorylated STAT3 and E2F3 was seen in GAS5 overexpressed cells, both of which could be increased by siGAS5. The GAS5 deficiency also reduced miR‐21 target proteins TIMP3 and PDCD4 expressions. Taken together, the GAS5 expression level is inversely associated with malignancy, but positively associated with sensitivity to cisplatin‐induced apoptosis, suggesting that GAS5 could be a biomarker of cisplatin‐resistance in clinical therapy of human cervical cancer.

Long Non-coding RNA Gas5 Is Associated With Preeclampsia and Regulates Biological Behaviors of Trophoblast via MicroRNA-21

“…GAS5 can act as the molecular spongy binding numerous microRNAs mutually but the observations in detail are still remained largely unclear. Negative regulation between GAS5 and microRNA-21 (miR-21) has been certificated in various tumors and other diseases for the GAS5 Exon 4 contains miR-21 binding sequence (Zhang et al, 2013;Song et al, 2014;Hu et al, 2016;Cao et al, 2017;Tao et al, 2017;Suo et al, 2018;Yao et al, 2019).…”

<p>Novel Tumor Suppressor lncRNA Growth Arrest-Specific 5 (GAS5) In Human Cancer</p>

“…82 GAS5 prohibited cell proliferation, colony formation, migration and invasion, and increased cell cycle arrest in Hela and Siha CC cells. 119 Overexpression of GAS5 inhibited cell proliferation, migration and invasion, induced cell apoptosis, and arrested cell cycle in A498 RCC cells as well. 35 Oral squamous cell carcinoma (OSCC) is the most common cancer of HNC.…”

“…84 Moreover, GAS5 enhanced the activity of DPP-induced cell growth inhibition and apoptosis in DPP-resistance cell via GAS5/miR-21/E2F transcription factor 3 (E2F3)/STAT pathway in CC, suggesting that GAS5 could be a novel target for CC patients with DPP-resistance in clinical. 119 Overexpression of GAS5 enhanced radio-sensitivity in SiHa CC cells, while GAS5 knockdown decreased radiosensitivity in ME180 CC cells. 130 In-depth mechanism studies showed that GAS5 enhanced the radio-sensitivity of CC cells via inducing immediate early response 3 (IER3) through regulation of miR-106b expression.…”

<p>Inhibition of TRIM32 Induced by miR-519d Increases the Sensitivity of Colorectal Cancer Cells to Cisplatin</p>

“…Thus, cisplatin destroys the normal function of DNA in cancer cells and induces cells to enter the apoptotic process. 24,25 However, high-dose treatment of cisplatin causes severe side effects, including neurotoxicity, nephrotoxicity, gastrointestinal reactions and myelosuppression. 26,27 Therefore, reducing the dosage of cisplatin and increasing the sensitivity of CRC cells to cisplatin is important to improve the chemotherapy effect and patient compliance.…”