Cancer Management and Research (Jul 2020)
miR-4429 Regulates the Proliferation, Migration, Invasion, and Epithelial-Mesenchymal Transition of Cervical Cancer by Targeting FOXM1
Abstract
Lin Liang,1– 3 Yu Wei Zheng,1– 3 Yan Li Wang1– 3 1Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China; 3Institute of Pathology, Fudan University, Shanghai 200032, People’s Republic of ChinaCorrespondence: Yu Wei ZhengDepartment of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of ChinaTel +86- 21-64175590Email [email protected] Li WangDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of ChinaTel +86- 21-64175590Email [email protected]: miR-4429 acts as an inhibitor in many malignant tumors and participates in the biological processes of them, but the clinical value and potential molecular mechanism of miR-4429 in cervical cancer (CC) are still under investigation.Objective: To analyze the clinical value and molecular mechanism of miR-4429 in CC.Materials and Methods: A qRT-PCR assay was employed to determine the levels of miR-4429 and forkhead-box M1 (FOXM1) in CC tissues, CC cell lines (SiHa, CaSki, ME-180, and C33A) and human normal immortalized epithelial cell lines (HaCaT). The proliferation, migration, invasion, and apoptosis abilities of ME-180 and C33A cells were detected, and the epithelial-to-mesenchymal transition (EMT)-related proteins in the cells were also determined.Results: MiR-4429 acted as a tumor suppressor gene in CC tissues and cells and was linked to lymph node metastasis and International Federation of Gynecology and Obstetrics (FIGO) staging. The survival analysis revealed that lymph node metastasis, high FIGO staging, and low miR-4429 expression were all related to the unfavorable prognosis of the patients, and the dual-luciferase reporter assay revealed that FOXM1 was the target of miR-4429. Both overexpression of miR-4429 and knock-down of FOXM1 inhibited the proliferation, migration, invasion, and EMT of CCCs, and accelerated the apoptosis of them. Conversely, both knockdown of miR-4429 and overexpression of FOXM1 promoted those biological behaviors of the cells. Moreover, the rescue experiment revealed that the overexpression of FOXM1 reversed the influences of miR-4429 overexpression on the proliferation, migration, invasion, and EMT of CCCs.Conclusion: miR-4429 acts as a tumor suppressor in CC and can directly target FOXM1 to regulate the proliferation, migration, invasion, apoptosis and EMT of CCCs, so miR-4429 is expected to be a new therapeutic target for CC.Keywords: miR-4429, FOXM1, cervical cancer, cell, biological behavior
