LncRNA HOTAIR acts as competing endogenous RNA to control the expression of Notch3 via sponging miR-613 in pancreatic cancer

Abstract

Pancreatic cancer is one of the most deadly cancers with a poor prognosis. Though studies have implicated the roles of microRNAs in pancreatic cancer progression, little is known about the role of miR-613 in pancreatic cancer. In the present study, the expression of miR-613 was down-regulated in pancreatic cancer tissues and cancer cell lines. Down-regulation of miR-613 was positively correlated with tumor differentiation, advanced TNM stage, nodal metastasis and shorter overall survival in patients with pancreatic cancer. Overexpression of miR-613 suppressed cell proliferation, invasion and migration, and induced cell apoptosis and cell cycle arrest at G0/G1 phase in pancreatic cancer cells. Bioinformatics analysis, luciferase reporter assay and rescue experiments showed that notch3 was a direct target of miR-613. MiR-613 was inversely correlated with notch3 expression in pancreatic cancer tissues. The long non-coding RNA, HOX transcript antisense RNA (HOTAIR) was up-regulated in both pancreatic cancer tissues and cancer cell lines, and HOTAIR suppressed the expression of miR-613 via functioning as a competing endogenous RNA. In vivo studies showed that stable overexpression of miR-613 or knock-down of HOTAIR suppressed tumor growth and also reduced the expression of notch3. In conclusion, these results suggest that HOTAIR functions as a competing endogenous RNA to regulate notch3 expression via sponging miR-613 in pancreatic cancer.

MEG3 Suppresses Human Pancreatic Neuroendocrine Tumor Cells Growth and Metastasis by Down-Regulation of Mir-183

“…An increasing literature has evidenced that lncRNA can act as a ceRNA via sponging miRNA [13, 14]. Herein, we detected the cross-regulation between MEG3 and miR-183, since in a recent review, miR-183 has been reported as a pivotal miRNA in endocrine cancer metastasis [21].…”

“…In the cancer studies, miRNAs can function to be oncogenic or tumor-suppressive [13]. Besides, an increasing study have evidenced that lncRNAs can act as a competing endogenous RNA (ceRNA) via sponging miRNAs [13, 14].…”

“…In the cancer studies, miRNAs can function to be oncogenic or tumor-suppressive [13]. Besides, an increasing study have evidenced that lncRNAs can act as a competing endogenous RNA (ceRNA) via sponging miRNAs [13, 14]. In previous studies, MEG3 has been described to be a ceRNA that regulate miR-21 [15, 16], miR-1297 [17], and miR-140-5p [18].…”

LncRNA HOTAIR/miR‐613/c‐met axis modulated epithelial‐mesenchymal transition of retinoblastoma cells

“…For example, HOTAIR could bind to inter‐cellular miR‐331‐3p and miR‐124 based on its characteristic RNA sponging, thereby up‐regulating cancer cells’ capacity to reproduce 26. The sponging relationship between HOTAIR and miR‐613 was also manifested within carcinomas, such as non‐small cell lung cancer and pancreatic cancer 27, 28. The miR‐613 herein was suggested as a suppressor for retinoblastoma formation by targeting E2F5 29.…”

Comprehensive Analysis of Differentially Expressed Profiles of lncRNAs/mRNAs and miRNAs with Associated ceRNA Networks in Triple-Negative Breast Cancer

“…The aberrantly expressed lncRNAs have been found to be implicated in tumorigenesis and development of various cancers, including breast cancer [5]. Some wellstudied lncRNAs, such as H19, MALAT1 and HOTAIR have been reported to play oncogenic roles in the pathogenesis of tumors [6][7][8], whereas MEG3, GAS5 and BANCR could function as tumor suppressors [9][10][11]. However, the molecular mechanisms of lncRNAs underlying carcinogenesis and progression of triple-negative breast cancer remain largely unknown.…”