Long Noncoding RNA GAS5, Which Acts as a Tumor Suppressor via microRNA 21, Regulates Cisplatin Resistance Expression in Cervical Cancer

Abstract

ObjectivesThe aims of this study were to investigate the functions of GAS5 as a tumor suppressor in cervical cancer and explore the mechanism.MethodsThe expression of GAS5 and microRNA 21 (miR-21) was detected in primary cervical cancer tissue specimens, as well as in cervical cancer cell lines. We identified the interaction of GAS5 and miR-21 by quantitative polymerase chain reaction, Western blot, and dual-luciferase reporter assay. We also studied the functions of GAS5 in proliferation, apoptosis, migration, and invasion in cervical cancer cells in vitro and vivo. Finally, the impact of GAS5 on cisplatin resistance and its mechanism in cervical cancer cells was also identified.ResultsThe expression of GAS5 and miR-21 was detected in primary cervical cancer tissue specimens, as well as in cervical cancer cell lines. GAS5, which is a tumor suppressor playing roles in inhibiting the malignancy of cervical cancer cells, including proliferation in vivo and vitro, migration, and invasion, has a low expression in cervical cancer tissue and cervical cancer cell lines, whereas miR-21 expression is high. GAS5 significantly decreased the expression of miR-21, and there is a reciprocal repression of gene expression between GAS5 and miR-21. Besides, most importantly, we found that high expression of GAS5 and low expression of miR-21 can enhance the sensitivity of SiHa/cDDP cancer cells to cisplatin. A further experiment for identifying the mechanism of cisplatin resistance by GAS5 showed that GAS5 can not only regulate phosphatase and tensin homolog through miR-21 but also influence the phosphorylation of Akt.ConclusionsOur results indicate that GAS5 is a direct target of miR-21 and can predict the clinical staging of cervical cancer. Most importantly, GAS5 can also influence cisplatin resistance in cervical cancer via regulating the phosphorylation of Akt. All of these suggest that GAS5 may be a novel therapeutic target for treating cervical cancer.

Long Non-Coding RNA SH3PXD2A-AS1 Promotes Cell Progression Partly Through Epigenetic Silencing P57 and KLF2 in Colorectal Cancer

“…Recently, dysregulation of lncRNAs has been reported to alter many biological processes, including cell cycle, proliferation, apoptosis, invasion, and epigenetic regulation [8-10]. Furthermore, lncRNAs are capable of exerting oncogenic or tumor-suppressive roles, and could be considered as diagnostic or therapeutic targets for patients with cancer [11-14]. Human CRC-specific lncRNA CCAT1-L enhances MYC expression and promotes tumorigenesis in CRC [15].…”

Long noncoding RNA FOXD2‐AS1 promotes glioma cell cycle progression and proliferation through the FOXD2‐AS1/miR‐31/CDK1 pathway

“…Recent reports have shown that lncRNAs and protein‐coding messenger RNAs are interacted by competing for shared miRNAs, that is, the ceRNA hypothesis . For example, GAS5 ncRNA upregulates PTEN by sponging miR‐21 or miR‐222, thereafter inhibiting tumor growth by activating the PTEN/AKT pathway . lncRNA ROR is able to regulate the reprogramming of pluripotent stem cells by modulating stem cell factors OCT4, NANOG, and SRY‐box 2 as a ceRNA .…”

Long Non-Coding RNA XLOC_006753 Promotes the Development of Multidrug Resistance in Gastric Cancer Cells Through the PI3K/AKT/mTOR Signaling Pathway

“…Furthermore, Liang et al reported that lncRNA LINP1 is upregulated in doxorubicin-and 5-fluorouracil-resistant cells and induced chemoresistance, indicating LINP1 is a potential therapeutic target and may be key to reducing chemoresistance in breast cancer (BC) [30]. Wen et al showed that lncRNA GAS5 could influence cisplatin resistance in cervical cancer (CC) by regulating the phosphorylation of Akt [31]. Xue et al found that lncRNA HOTAIR is upregulated in tamoxifen-resistant BC tissues; its overexpression increased BC cell proliferation and conferred tamoxifen resistance in BC [32].…”