Abstract
Accumulating evidence highlights the fact that long non‑coding RNAs (lncRNAs) serve as critical factors in the growth of hepatocellular carcinoma (HCC). The dysregulation of lncRNA KCNQ1 opposite strand/antisense transcript1 (KCNQ1OT1) has been reported in numerous human benign diseases. However, the role of KCNQ1OT1 in human HCC remains poorly understood. In this study, we demonstrated that the expression of KCNQ1OT1 was abnormally increased in HCC tissues. The ectopic high expression of KCNQ1OT1 was associated with liver cirrhosis, a larger tumor size, an advanced TNM stage, and a worse overall survival and tumor‑free survival. For the first time, to the best of our knowledge, we report that KCNQ1OT1 knockdown results in a decreased cell viability and colony formation ability, and an increased rate of apoptosis invitro. The results from our invivo results demonstrated that KCNQ1OT1 silencing attenuated tumor growth by impairing cell proliferation. Additionally, we found that KCNQ1OT1 exerted its effects partly by relying on the microRNA‑504 (miR‑504)‑mediated regulation of cyclin‑dependent kinase16 (CDK16), in addition to the regulation of the glycogen synthase kinase3β (GSK3β)/β‑catenin/Bcl‑2 signaling pathway. The present study revealed the functions and mechanisms of action of lncRNA KCNQ1OT1 regarding its role in promoting the growth of HCC. Thus, lncRNA KCNQ1OT1 may prove to be a potential therapeutic target for human HCC.
Highlights
Hepatocellular carcinoma (HCC) remains a serious health burden worldwide [1]
Long non‐coding RNAs are a class of abundant and largely uncharacterized non‐protein‐coding RNAs that are >200 nucleotides in length [4]. lncRNAs have been demonstrated to regulate cell proliferation in HCC [5]. lncRNA TUG1 has been shown to promote HCC growth in vitro and in vivo by epigenetically suppressing Kruppel‐like factor 2 (KLF2) transcription [6]. lncRNA HOTAIR has been shown to increase cell viability by enhancing glucose transporter isoform 1 (GLUT1)‐mediated glycolysis [7]. lncRNA KCNQ1 opposite strand/antisense transcript 1 was initially identified as an aberrantly expressed lncRNA in Beckwith‐Wiedemann syndrome, which is an overgrowth disorder usually presenting in the embryonic stages [8]
We found that KCNQ1OT1 expression was significantly increased in the HCC tissues compared with in the adjacent non‐tumor tissues (Fig. 1A, P
Summary
Hepatocellular carcinoma (HCC) remains a serious health burden worldwide [1]. In China, >466,100 new cases andKey words: lncRNA KCNQ1OT1, hepatocellular carcinoma, growth, microRNA-504, CDK16422,100 HCC‐associated deaths were reported in 2015 [2]. Clinical experience indicates that patients affected by tumors of a large size usually have a poor prognosis [3]. LncRNA TUG1 has been shown to promote HCC growth in vitro and in vivo by epigenetically suppressing Kruppel‐like factor 2 (KLF2) transcription [6]. A high KCNQ1OT1 expression has been shown to be associated with a large tumor size [9]. KCNQ1OT1 silencing by this drug induced the death of Wilms' tumor‐derived G401 cells [10]. These results indicate that KCNQ1OT1 may be a novel therapeutic target for patients with high intra‐tumoral levels of KCNQ1OT1
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