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The lncRNA-HOXA-AS2/EZH2/LSD1 oncogene complex promotes cell proliferation in pancreatic cancer.

ABSTRACT: Emerging evidence have indicated that long non-coding RNAs (lncRNAs) play crucial roles in cancer development and progression. Previous studies have suggested that lncRNA-HOXA cluster antisense RNA 2 (HOXA-AS2) is involved in tumorigenesis of several cancers. However, little is known about the alteration and biological functions of HOXA-AS2 in pancreatic cancer (PC). The purpose of this study is to identify the role of HOXA-AS2 in PC. Here, we provided evidence that lncRNA HOXA-AS2 was up-regulated in PC tissues. In addition, Loss-of-function experiments revealed that HOXA-AS2 knockdown effectively suppressed proliferation by blocking the cell cycle transition and caused apoptosis of PC cells in vitro and in vivo. Mechanistically, we found that HOXA-AS2 directly interacted with enhancer of zeste homolog 2 (EZH2) and lysine specific demethylase 1 (LSD1), which promoted PC cell growth ability. Collectively, our findings demonstrated that lncRNA-HOXA-AS2/EZH2/LSD1 complex may function as an oncogene in PC cell proliferation, and also provides a potential therapy target for PC.

SUBMITTER: Lian Y

PROVIDER: S-EPMC5752899 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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The lncRNA-HOXA-AS2/EZH2/LSD1 oncogene complex promotes cell proliferation in pancreatic cancer.

Lian Yifan Y Li Zhaohua Z Fan Yanyun Y Huang Qingwen Q Chen Jianmin J Liu Wenming W Xiao Chuanxing C Xu Hongzhi H

American journal of translational research 20171215 12

Emerging evidence have indicated that long non-coding RNAs (lncRNAs) play crucial roles in cancer development and progression. Previous studies have suggested that lncRNA-HOXA cluster antisense RNA 2 (HOXA-AS2) is involved in tumorigenesis of several cancers. However, little is known about the alteration and biological functions of HOXA-AS2 in pancreatic cancer (PC). The purpose of this study is to identify the role of HOXA-AS2 in PC. Here, we provided evidence that lncRNA HOXA-AS2 was up-regula ...[more]

PMID: 29312501

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Project description:To explore the function and mechanism of lncRNA HOXA-AS2 in cancer-associated fibroblasts (CAFs)-derived exosomes in gallbladder cancer metastasis, and provide new research targets for the treatment of gallbladder cancer. At the same time, in order to clarify the early predictive value of lncRNA HOXA-AS2 for gallbladder cancer metastasis, and to provide a theoretical basis for clinical individualized treatment of gallbladder cancer. Methods. In our previous work, we used TCGA database analysis to find that lncRNA HOXA-AS2 was highly expressed in gallbladder cancer tissues compared with normal tissues. In this study, the expression levels of HOXA-AS2 in gallbladder cancer cell lines and control cells were first verified by QPCR and Western blot methods. Then, lentiviral tools were used to construct knockdown vectors (RNAi#1, RNAi#2) and negative control vectors targeting two different sites of HOXA-AS2, and the vectors were transfected into NOZ and OCUG-1 cells, respectively. Real-time PCR was used to detect knockdown efficiency. Then, the effects of silencing HOXA-AS2 on the proliferation, cell viability, cell migration, and invasion ability of gallbladder cancer cells were detected by MTT, plate cloning assay, Transwell migration chamber assay, and Transwell invasion chamber assay. Finally, the interaction between HOXA-AS2 and miR-6867 and the 3'UTR of YAP1 protein was detected by luciferase reporter gene. The results showed that the expression level of HOXA-AS2 in gallbladder cancer cell lines was higher than that in control cells. The expression of HOXA-AS2 in gallbladder carcinoma tissues was significantly higher than that in adjacent tissues (p < 0.05). After successful knockout of HOXA-AS2 by lentiviral transfection, the expression of HOXA-AS2 in gallbladder cancer cell lines was significantly decreased. Through cell proliferation and plate clone detection, it was found that silencing HOXA-AS2 inhibited cell proliferation and invasion. Through software prediction and fluorescein reporter gene detection, it was found that HOXA-AS2 has a binding site with miR-6867, and the two are negatively correlated, that is, the expression of miR-6867 is enhanced after the expression of HOXA-AS2 is downregulated. And the 3'UTR of YAP1 protein in the Hippo signaling pathway binds to miR-6867. Therefore, HOXA-AS2 may affect the expression of YAP1 protein by regulating miR-6867, thereby inhibiting the Hippo signaling pathway and promoting the proliferation and metastasis of gallbladder cancer cells. HOXA-AS2 is abnormally expressed in gallbladder cancer cells. HOXA-AS2 may promote the migration and invasion of gallbladder cancer cells by regulating the Hippo signaling pathway through miR-6867. HOXA-AS2 may serve as a potential diagnostic and therapeutic target for gallbladder cancer in clinic.

Dataset Information

The lncRNA-HOXA-AS2/EZH2/LSD1 oncogene complex promotes cell proliferation in pancreatic cancer.

Publications

The lncRNA-HOXA-AS2/EZH2/LSD1 oncogene complex promotes cell proliferation in pancreatic cancer.

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