Dysregulation of KCNQ1OT1 promotes cholangiocarcinoma progression via miR-140-5p/SOX4 axis

Hongwei Sun; Ying Li; Hongru Kong; Shengjie Dai; Haixin Qian

doi:10.1016/j.abb.2018.09.019

Dysregulation of KCNQ1OT1 promotes cholangiocarcinoma progression via miR-140-5p/SOX4 axis

Arch Biochem Biophys. 2018 Nov 15:658:7-15. doi: 10.1016/j.abb.2018.09.019. Epub 2018 Sep 21.

Authors

Hongwei Sun¹, Ying Li², Hongru Kong³, Shengjie Dai³, Haixin Qian⁴

Affiliations

¹ Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, China.
² Department of Operating Room, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, China.
³ Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, China.
⁴ Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, China. Electronic address: HaixinHaixinQian19@163.com.

PMID: 30243712
DOI: 10.1016/j.abb.2018.09.019

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.

Keywords: Cholangiocarcinoma; KCNQ1OT1; Migration; Proliferation; SOX4; miR-140-5p.

MeSH terms

Apoptosis / genetics
Bile Duct Neoplasms / diagnosis
Bile Duct Neoplasms / genetics
Cell Line, Tumor
Cell Movement / genetics
Cell Proliferation / genetics
Cholangiocarcinoma / diagnosis
Cholangiocarcinoma / genetics*
Disease Progression*
Epithelial-Mesenchymal Transition / genetics
Female
Gene Expression Regulation, Neoplastic
Humans
Male
MicroRNAs / genetics*
Middle Aged
Potassium Channels, Voltage-Gated / genetics
Prognosis
RNA, Messenger / genetics*
SOXC Transcription Factors / genetics*
Up-Regulation

Substances

KCNQ1OT1 long non-coding RNA, human
MicroRNAs
Mirn140 microRNA, human
Potassium Channels, Voltage-Gated
RNA, Messenger
SOX4 protein, human
SOXC Transcription Factors