RP11-81H3.2 Acts as an Oncogene via microRNA-490-3p Inhibition and Consequential Tankyrase 2 Up-Regulation in Hepatocell
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ORIGINAL ARTICLE
RP11‑81H3.2 Acts as an Oncogene via microRNA‑490‑3p Inhibition and Consequential Tankyrase 2 Up‑Regulation in Hepatocellular Carcinoma Wei Chen1 · Kang Li1 · Kun Zhu1 · Rong Yan1 · Qing‑Chun Cai1 · Wen‑Han Li1 · Cheng‑Xue Dang1 Received: 15 September 2019 / Accepted: 10 December 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract Background Hepatocellular carcinoma (HCC) is a serious threat to human lives and is usually diagnosed at the late stages. Recently, there has been a rapid advancement in the treatment options for HCC, but novel therapeutic targets are still needed, especially for precision medicine. Aims We aimed to investigate the involvement of non-coding RNA RP11-81H3.2 in HCC. Methods The expression of RP11-81H3.2 was examined in the blood samples of HCC patients, and in the human HCC cell lines, including HepG2, Smmc-7721, and Huh7. Cell proliferation was determined using the CCK-8 and EdU assay, and cell invasion and migration were determined using the transwell/wound healing assay. The effects of RP11-81H3.2 knockdown on in vivo tumor growth were evaluated utilizing the nude mice HepG2 tumor xenograft model. Results Here, we have identified a long non-coding RNA, RP11-81H3.2, which is enriched in HCC and can promote its proliferation, migration, and invasion both in vitro and in vivo. In addition, our results showed that RP11-81H3.2 binds to and regulate miR-490-3p expression in the HCC cells. Moreover, we found that RP11-81H3.2 regulates the expression of TNKS2 via miR-490-3p. Further, we found that RP11-81H3.2 and miR-490-3p form a regulatory loop; the release of RP11-81H3.2 leads to the suppression of miR-490-3p expression, thus, further enhancing the expression of RP11-81H3.2. Conclusions Our data have provided a novel target for the diagnosis and treatment of HCC, and sheds light on the lncRNA– miRNA regulatory nexus that can control the HCC related pathogenesis. Keywords Hepatocellular carcinoma · Long non-coding RNA · RP11-81H3.2 · microRNA · miR-490-3p · TNKS2
Introduction As the most common primary malignant tumor of the liver, hepatocellular carcinoma (HCC) is the third leading cause of cancer related deaths worldwide [1]. Since most HCC patients are diagnosed with HCC at an advanced stage [2], it is necessary that the researchers identify critical regulators involved in the development of HCC. Among the various risk factors for HCC, genetic factors play crucial roles in the progression of HCC [3]. The situation in China is worse since over 50% of the HCC cases diagnosed worldwide are * Cheng‑Xue Dang [email protected] 1
Department of Surgical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China
from China [4]. Recently, accumulating evidences have shown that previously ignored long non-coding RNAs (lncRNAs) play essential roles in HCC [5]. The non-coding RNA H19 and insulin-like growth factor II (IGF2) were initially characterized as showing aberrant expression in HCC, e
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