Knockdown of PVT1 Suppresses Colorectal Cancer Progression by Regulating MiR-106b-5p/FJX1 Axis

Cancer Management and Research

关键词: colorectal cancer;    pvt1;    mir-106b-5p;    fjx1;    metastasis;    apoptosis;   

DOI  :  

来源: DOAJ

【 摘 要 】

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 [phone]Email [e-mail]: 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

【 授权许可】

Unknown