MicroRNA-193a-3p suppresses the colorectal cancer cell proliferation and progression through downregulating the PLAU expression
Received 10 March 2019
Accepted for publication 21 May 2019
Published 12 June 2019 Volume 2019:11 Pages 5353—5363
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Antonella D'Anneo
Maosong Lin,1 Zan Zhang,1 Mingjun Gao,1 Hong Yu,2 Haihui Sheng,3 Junxing Huang4
1Department of Gastroenterology, Taizhou People’s Hospital, Taizhou, Jiangsu 225300, People’s Republic of China; 2Department of Pathology, Taizhou People’s Hospital, Taizhou, Jiangsu 225300, People’s Republic of China; 3Shanghai Engineering Center of Molecular Medicine, and National Engineering Center for Biochip, Shanghai 201203, People’s Republic of China; 4Department of Oncology, Taizhou People’s Hospital, Taizhou, Jiangsu 225300, People’s Republic of China
Background: Colorectal cancer (CRC) is one of the leading causes of cancer-related death in China. Dysregulation of microRNAs (miRNAs) is involved in cancer development and progression. Our previous study showed an inverse relationship between miR-193a-3p expression and the prognosis of CRC. However, the exact biological functions of miR-193a-3p in CRC are still poorly understood. This study aimed to explore the role and mechanism of miR-193a-3p in CRC.
Methods: Real-time PCR and Western blotting were used to examine the expression levels of RNA and protein, respectively. A dual luciferase assay was performed to validate predicted targets of miR-193a-3p. Loss and gain-of-function studies were carried out to reveal the effects and potential mechanism of the miR-193a-3p in the proliferation, metastasis and angiogenesis of CRC cells.
Results: The expression levels of miR-193a-3p in human CRC cell lines were significantly decreased compared with that in normal colonic epithelium cell line. Furthermore, plasminogen activator urokinase (PLAU) was validated as a direct target gene of miR-193a-3p. Over-expression of miR-193a-3p inhibited proliferation, migration and angiogenesis of HT-29 cell, whereas forced expression of PLAU could rescue the inhibitory effects.
Conclusion: miR-193a-3p might inhibit CRC cell growth, migration and angiogenesis partly through targeting PLAU. MiR-193a-3p/PLAU axis might provide a potent therapeutic opportunity for aggressive CRC.
Keywords: microRNA-193a-3p, colorectal cancer, PLAU, cell proliferation, invasion, angiogenesis
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