Search

The identification and characterization of long non‐coding RNAs (lncRNAs) in diverse biological process has currently developed rapidly. LncRNA‐PVT1, located adjacent to the MYC locus on chromosomal region 8q24, has been reported to be associated with many biological processes. However, the function and mechanism of PVT1 in pancreatic carcinoma (PC) is poorly understood. In this present study, we first measured the level of PVT1 in the PC cell lines and tissues by quantitative real‐time PCR (qRT‐PCR), and then employed loss‐of‐function and gain‐of‐function approaches to explore the association between PVT1 expression levels and PC cell proliferation/migration ability. Furthermore, bioinformatics analysis was utilized to show that PVT1 contains binding site for miR‐448 and an inverse correlation between PVT1 and miR‐448 was obtained in PC specimens. Additionally, dual luciferase reporter assay, RNA‐binding protein immunoprecipitation (RIP) and applied biotin‐avidin pulldown system were applied to further confirm that PVT1 directly bind with microRNA binding site harboring in the PVT1 sequence. Then, SERBP1 was identified as a target of miR‐448 according to the gene expression array analysis of PC clinical samples. Together, we revealed that PVT1 functions as an endogenous “sponge” by competing for miR‐448 binding to regulate the miRNA target SERBP1 and, therefore, promotes the proliferation and migration of PC cells. [ABSTRACT FROM AUTHOR]

Abstract It is commonly recognized that aberrant expression of long non-coding RNAs (lncRNAs) is an important cause of cancer progression. The oncogenic property of KCNQ1OT1 has been identified in several malignant tumors. Here, we decided to explore the biological function and molecular mechanism of KCNQ1OT1 in cholangiocarcinoma (CCA). The expression conditions of KCNQ1OT1 in different tissues and cell lines were examined with qRT-PCR analysis. As expected, KCNQ1OT1 was highly expressed in CCA tissues and cell lines. Results of functional assays revealed the oncogenic function of KCNQ1OT in cholangiocarcinoma progression. The positive effect of KCNQ1OT1 on cell proliferation, invasion and epithelial-mesenchymal transition was identified by performing MTT assay, colony formation assay, transwell invasion assay and western blotting. Whereas, the negative effect of KCNQ1OT1 on the cell apoptosis was tested with flow cytometry analysis. Mechanism investigation revealed that KCNQ1OT1 can act as a ceRNA to improve CCA progression by regulating miR-140-5p/SOX4 axis. Recue assays were conducted to demonstrate the actual effects of KCNQ1OT1-miR-140-5p-SOX4 pathway on CCA progression. Highlights • Overexpressed KCNQ1OT1 is a prognostic factor for CCA patients. • The inhibitory effects of silenced KCNQ1OT1 on proliferation, EMT progress and invasion of CCA cells. • KCNQ1OT1 upregulates SOX4 through competitively binding with miR-140-5p. • KCNQ1OT1 improves CCA progression in a miR-140-5p/SOX4 dependent manner. [ABSTRACT FROM AUTHOR]