Inhibiting effect of MicroRNA-3619-5p/PSMD10 axis on liver cancer cell growth in vivo and in vitro

• Published in: Life sciences (1973) Vol. 254; pp. 117632 - 10
• Main Authors: Hao, Peipei, Yue, Fengming, Xian, Xian, Ren, Qian, Cui, Huixian, Wang, Yunpeng
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.08.2020; Elsevier BV
• Subjects: Antigens; Cancer; Cell cycle; Cell growth; Cell proliferation; Cyclin A; Cyclin D1; Cyclin E; Flow cytometry; G1 phase; Hepatocytes; Immunofluorescence; Immunohistochemistry; Liver; Liver cancer; MicroRNAs; miR-3619-5p; miRNA; Overexpression; Phosphorylation; Proliferating cell nuclear antigen; Proteins; PSMD10; Retina; Retinoblastoma; Retinoblastoma protein; Stat3 protein; Transcription; PSMD10; Cell proliferation; Liver cancer; miR-3619-5p
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2020.117632

Liver cancer is one of the leading causes of cancer death worldwide owing to its delayed diagnosis and absence of efficient treatment at advanced TNM stages. Increasing evidence demonstrated that microRNAs are implicated in tumorgenesis and cancer development by regulating cancer-related proteins. This study aimed to explore the effect of miR-3619-5p on cell growth in liver cancer. The effect of miR-3619-5p on cell proliferation was measured by quantitative real-time PCR, MTT assay, flow cytometry, and Immunofluorescence assay. The interaction between miR-3619-5p and PSMD10 was validated using dual-luciferase. The expression of PSMD10 and Ki67 was further determined by immunohistochemistry. MiR-3619-5p over-expression remarkably inhibited cell proliferation and induced G1 phase arrest, accompanied with reduced expression of proliferating cell nuclear antigen. The expression of miR-3619-5p was negatively correlated to that of PSMD10, and PSMD10 was validated to be a downstream target of miR-3619-5p. Moreover, miR-3619-5p induced suppressed proliferation and G1 phase arrest were abrogated by elevated the expression of PSMD10 in liver cancer cells. PSMD10 over-expression also induced phosphorylation of signal transducer and activator of transcription 3 (STAT3) and retinoblastoma protein (Rb1). Besides, elevated cyclin A, cyclin D1 and cyclin E expression supported that PSMD10 promoted the progress of cell cycle. In addition, miR-3619-5p inhibited tumor growth in vivo by targeting PSMD10, accompanied with blocked cell cycle. In conclusion, our findings revealed that miR-3619-5p inhibits cancer cell proliferation by targeting PSMD10, and miR-3619-5p as a potential therapeutic target for the treatment of liver cancer.