Abstract
Sevoflurane (SEVO) is widely applied as an anesthetic, which exerts antitumor capacity in various cancers, including hepatocellular carcinoma (HCC). Previous studies indicated that long non-coding RNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) was upregulated, while microRNA-29a-3p (miR-29a-3p) was downregulated in HCC. Thus, we aimed to explore the roles of KCNQ1OT1 and miR-29a-3p in HCC cells exposed to SEVO. Cell proliferation, apoptosis, migration, and invasion were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and transwell assays, respectively. The levels of genes were determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Furthermore, the interaction between miR-29a-3p and KCNQ1OT1 or chromebox protein homolog 3 (CBX3) was predicted by Starbase or Targetscan, and then confirmed by dual-luciferase reporter assay. We found that the levels of KCNQ1OT1 and CBX3 were decreased, while miR-29a-3p was increased in SEVO-treated HCC cells. KCNQ1OT1 overexpression weakened the inhibitory effects of SEVO on HCC cell proliferation, apoptosis, migration, and invasion. Interestingly, KCNQ1OT1 bound to miR-29a-3p, and miR-29a-3p targeted CBX3. KCNQ1OT1 upregulated CBX3 level by repressing miR-29a-3p expression. Furthermore, KCNQ1OT1 exerted tumor promotion in HCC cells via suppressing miR-29a-3p to regulate CBX3 expression. Collectively, our findings demonstrated that KCNQ1OT1 regulated the antitumor effects of SEVO on HCC cells through modulating the miR-29a-3p/CBX3 axis, providing a theoretical basis for the treatment of HCC.
Highlights
Hepatocellular carcinoma (HCC) is one of the major causes of cancer-associated death worldwide [1]
We found that the promotion effects of SEVO on BCL2 associated X (Bax) and Cleaved-casp-3 expression as well as the inhibition effect on B-cell lymphoma 2 (Bcl-2) expression were abolished by miR-29a-3p inhibitor (Figure 4G and H)
SEVO has been used for the treatment of human cancers, including hepatocellular carcinoma (HCC) [19,20]. Long non-coding RNAs (lncRNAs) were identified to exert crucial roles in HCC development [21,22]
Summary
Hepatocellular carcinoma (HCC) is one of the major causes of cancer-associated death worldwide [1]. A report showed that there were more than 466,100 new cases of HCC and 422,100 HCC-related deaths in China in 2015 [2]. The survival rate for HCC patients is still low due to the high incidence of metastasis [3]. Sevoflurane (SEVO), an anesthetic agent, is widely applied for clinical therapy of diseases and plays a suppressive role in various cancers [4]. SEVO can inhibit cell proliferation and cell cycle in breast cancer [5]. SEVO acted as a suppressor in lung carcinoma progression [6]. SEVO suppressed the development of HCC [7]. The detailed mechanisms of SEVO in HCC cells remain unclear
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