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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MiR-9-1 Suppresses Cell Proliferation and Promotes Apoptosis by Targeting UHRF1 in Lung Cancer
Cheng-You Jia1, Wei Xiang2, Ji-Bin Liu3
1Shanghai Tenth People's Hospital, 278245Tongji University School of Medicine, Shanghai, China.
Abstract:
Lung cancer is listed as the most common reason for cancer-related death all over the world despite diagnostic improvements and the development of chemotherapy and targeted therapies. MicroRNAs control both physiological and pathological processes including development and cancer. A microRNA-9 to 1 (miR-9 to 1) overexpression model in lung cancer cell lines was established and miR-9 to 1 was found to significantly suppress the proliferation rate in lung cancer cell lines, colony formation in vitro, and tumorigenicity in nude mice of A549 cells. Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) was then identified to direct target of miR-9 to 1. The inhibition of UHRF1 by miR-9 to 1 causes G1 arrest and p15, p16, and p21 were re-expressed in miR-9 to 1 group in mRNA level and protein level. Silence of UHRF1 expression in A549 cells resulted in the similar re-expression of p15, p16, p21 which is similar with miR-9 to 1 infection. Therefore, we concluded that UHRF1 is a new target for miR-9 to 1 to suppress cell proliferation by re-expression of tumor suppressors p15, p16, and p21 mediated by UHRF1.
Insights
MicroRNA-9 to 1 (miR-9 to 1) suppresses lung cancer growth by targeting UHRF1. This leads to cell cycle arrest and re-expression of tumor suppressors p15, p16, and p21, offering a new therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Lung cancer remains a leading cause of cancer mortality globally.
- MicroRNAs (miRNAs) play crucial roles in cellular processes, including cancer development.
- Existing treatments for lung cancer have limitations, necessitating novel therapeutic approaches.
Purpose of the Study:
- To investigate the role of microRNA-9 to 1 (miR-9 to 1) in lung cancer.
- To identify the molecular targets of miR-9 to 1 involved in lung cancer suppression.
- To elucidate the mechanism by which miR-9 to 1 inhibits lung cancer progression.
Main Methods:
- Overexpression of miR-9 to 1 in lung cancer cell lines (A549).
- Assessment of cell proliferation, colony formation in vitro, and tumorigenicity in vivo.
- Identification of UHRF1 as a direct target of miR-9 to 1 using molecular assays.
- Analysis of cell cycle regulators (p15, p16, p21) at mRNA and protein levels.
Main Results:
- Overexpression of miR-9 to 1 significantly suppressed lung cancer cell proliferation, colony formation, and tumorigenicity.
- Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) was identified as a direct target of miR-9 to 1.
- miR-9 to 1-mediated inhibition of UHRF1 led to G1 cell cycle arrest.
- Re-expression of tumor suppressor genes p15, p16, and p21 was observed at both mRNA and protein levels in the miR-9 to 1 group.
Conclusions:
- miR-9 to 1 acts as a tumor suppressor in lung cancer by targeting UHRF1.
- The miR-9 to 1/UHRF1 axis regulates cell proliferation through the re-expression of p15, p16, and p21.
- UHRF1 represents a novel therapeutic target for miR-9 to 1-based lung cancer treatment.
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