lncRNA KCNQ1OT1 reverses the effect of sevoflurane on hepatocellular carcinoma progression via regulating the miR-29a-3p/CBX3 axis

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.

Clinical Significance of Expression of CBX3 in Colorectal Cancer and its Possible Mechanism / 胃肠病学

Background:CBX3 is a member of heterochromatin protein family. Recent studies indicated that CBX3 was closely related to lung cancer,osteosarcoma,gastric cancer. Aims:To investigate the expression and clinical significance of CBX3 in colorectal cancer,and explore the potential mechanism. Methods:Thirty colorectal cancer patients from June 2011 to June 2012 at Shanghai Renji Hospital were enrolled. Real-time quantitative PCR and immunohistochemistry were used to determine mRNA and protein expressions of CBX3 in colorectal cancer tissues and corresponding paracancerous tissues, respectively. Human colorectal cancer cell line RKO was transfected with overexpressed plasmid or siRNA of CBX3. Cell proliferation was measured by CCK-8 assay,Western blotting was implemented to determine the protein expressions of CBX3 and p53. Results:The mRNA and protein expressions of CBX3 were significantly increased in colorectal cancer tissues than in corresponding paracancerous tissues. Increased protein expression of CBX3 was closely correlated with tumor size (P ＝ 0. 025 ),lymph node metastasis (P ＝ 0. 013 )and TNM staging (P ＝ 0. 020 ). After intervention with overexpressed plasmid of CBX3,the mRNA and protein expressions of CBX3 were efficiently upregulated in RKO cells, cell proliferation and protein expression of p53 were significantly increased. Meanwhile,the mRNA and protein expressions of CBX3 were efficiently downregulated in RKO cells after knockdown of CBX3,resulting in significantly decreased cell proliferation and protein expression of p53. Conclusions:CBX3 may promote the proliferation of colorectal cancer cells via influencing the expression of p53,thus promoting the progression of colorectal cancer. This indicates that CBX3 has the potential to be a new target for diagnosis and therapy of colorectal cancer.