Cancer Management and Research (Sep 2020)
Knockdown of PVT1 Suppresses Colorectal Cancer Progression by Regulating MiR-106b-5p/FJX1 Axis
Abstract
Fang Liu,1 Rong Wu,2 Lina Guan,3 Xuegui Tang1 1Anorectal Department of Integrated Traditional Chinese and Western Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 2Department of Clinical Medicine of Combination of Chinese and Western Medicine, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 3Institute of Anorectal Diseases, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of ChinaCorrespondence: Xuegui Tang Anorectal Department of Integrated Traditional Chinese and Western MedicineAffiliated Hospital of North Sichuan Medical College, No. 1, Maoyuan South Road, Nanchong 637000, Sichuan, People’s Republic of ChinaTel +86-0817-2262120Email [email protected]: Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) has been revealed to involve in the progression of CRC. However, the precise mechanisms of PVT1 in action remain unclear.Methods: The expression of PVT1, microRNA-106b-5p (miR-106b-5p) and four jointed box 1 (FJX1) was measured using quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot, respectively. Cell proliferation was investigated by 3-(4,5)-dimethylthiahiazo (−z-y1)-3,5-di-phenytetrazoliumromide assay. Transwell assay was used to determine cell migration and invasion. The correlation between miR-106b-5p and PVT1 or FJX1 was confirmed using luciferase reporter assay. The effects of PVT1 in vivo were assessed using mice xenograft model.Results: PVT1 was up-regulated in CRC tissues and cell lines, especially in CRC tissues with high-grade, and highly expressed PVT1 predicted worse prognosis. Functional experiments demonstrated that PVT1 deletion inhibited CRC cell proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. MiR-106b-5p was confirmed to be a target of PVT1, and inhibition of miR-106b-5p reversed the inhibitory effects of PVT1 knockdown on CRC cell malignant phenotypes. In addition, we found miR-106b-5p directly targeted FJX1, and miR-106b-5p-mediated inhibition on CRC cell proliferation, migration and invasion was attenuated by FJX1 up-regulation. Importantly, it was also proved that PVT1 could indirectly regulate FJX1 expression via targeting miR-106b-5p.Conclusion: Knockdown of PVT1 impaired cell proliferation, migration and invasion in CRCs via regulating miR-106b-5p/FJX1 axis, which provided a novel insight into the development of therapeutic strategies for CRC patients.Keywords: colorectal cancer, PVT1, miR-106b-5p, FJX1, metastasis, apoptosis
