Long Non-Coding RNA-PAICC Promotes the Tumorigenesis ofHuman Intrahepatic Cholangiocarcinoma byIncreasing YAP1 Transcription.

Long Xia,Jiarui Yang,Qi Yin,Hua Li,Shuguang Zhu,Haoqi Chen,Xiaolong Chen,Lei Zhang,Guihua Chen,Yueyu Hong

doi:10.3389/fonc.2020.595533

Abstract

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.

Highlights

Intrahepatic cholangiocarcinoma (ICC) is the common liver malignant tumor after hepatocellular carcinoma (HCC)
We further analyzed the expression of key genes in the Hippo pathway in GSE107943, and we found that the key effector gene, Yes-associated protein (YAP1) and its homologous transcriptional coactivator, TAZ, were significantly elevated in ICC tissues (Figure 1D, a–b)
We identified that the expression of the novel Long non-coding RNAs (lncRNAs), lncRNA-PAICC, was upregulated in human ICC specimens through data mining

Summary

Introduction

Intrahepatic cholangiocarcinoma (ICC) is the common liver malignant tumor after hepatocellular carcinoma (HCC). Despite advances in ICC standards of care and management options, the prognosis of this devastating cancer is still poor. The poor prognosis and high recurrence rate of ICC. Only approximately 30–40% of ICC patients have the opportunity to receive surgery, and the 5-year survival rate is only 20–40%. For patients with unresectable and recurring ICC, standard chemotherapy regimens (gemcitabine and cisplatin) are only palliative treatments, resulting in limited survival benefits [2, 3]. In contrast to hepatocellular carcinoma, no specific targeted molecular therapy for ICC has been approved so far, and limited clinical trials of targeted therapy for ICC have ended in failure [4, 5], thereby emphasizing the urgency of identifying new therapeutic targets for successful intervention

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Results

Conclusion