Xia Long, Chen Xiaolong, Yang Jiarui, Zhu Shuguang, Zhang Lei, Yin Qi, Hong Yueyu, Chen Haoqi, Chen Guihua, Li Hua
Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Department of Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Front Oncol. 2021 Jan 8;10:595533. doi: 10.3389/fonc.2020.595533. eCollection 2020.
Intrahepatic cholangiocarcinoma (ICC) is a heterogeneous hepatobiliary tumor with poor prognosis, and it lacks reliable prognostic biomarkers and effective therapeutic targets. Long non-coding RNAs (lncRNAs) have been documented to be involved in the progression of various cancers. However, the role of lncRNAs in ICC remains largely unknown. In the present work, we used bioinformatics analysis to identify the differentially expressed lncRNAs in human ICC tissues, among which lncRNA-PAICC was found to be an independent prognostic marker in ICC. Moreover, lncRNA-PAICC promoted the proliferation and invasion of ICC cells. Mechanistically, lncRNA-PAICC acted as a competitive endogenous RNA (ceRNA) that directly sponged the tumor suppressive microRNAs miR-141-3p and miR-27a-3p. The competitive binding property was essential for lncRNA-PAICC to promote tumor growth and metastasis through activating the Hippo pathway. In summary, our results highlighted the important role of the lncRNA-PAICC-miR-141-3p/27a-3p-Yap1 axis in ICC, which offers a novel perspective on the molecular pathogenesis and may serve as a potential target for antimetastatic molecular therapies of ICC.
肝内胆管癌(ICC)是一种预后较差的异质性肝胆肿瘤,且缺乏可靠的预后生物标志物和有效的治疗靶点。长链非编码RNA(lncRNA)已被证明参与多种癌症的进展。然而,lncRNA在ICC中的作用仍 largely未知。在本研究中,我们使用生物信息学分析来鉴定人类ICC组织中差异表达的lncRNA,其中lncRNA-PAICC被发现是ICC中的一个独立预后标志物。此外,lncRNA-PAICC促进了ICC细胞的增殖和侵袭。机制上,lncRNA-PAICC作为一种竞争性内源性RNA(ceRNA),直接吸附肿瘤抑制性微小RNA miR-141-3p和miR-27a-3p。这种竞争性结合特性对于lncRNA-PAICC通过激活Hippo通路促进肿瘤生长和转移至关重要。总之,我们的结果突出了lncRNA-PAICC-miR-141-3p/27a-3p-Yap1轴在ICC中的重要作用,这为分子发病机制提供了新的视角,并可能作为ICC抗转移分子治疗的潜在靶点。