miR-140-3p impedes the proliferation of human cervical cancer cells by targeting RRM2 to induce cell-cycle arrest and early apoptosis |
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| Affiliation: | 1. Department of Oral and Maxillofacial Surgery, School of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran;2. Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;3. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;1. Department of Molecular Medicine, University of Padova, I-35121 Padova, Italy;2. Department of Medicine, University of Padova, I-35121 Padova, Italy;3. Veneto Institute of Oncology IOV IRCCS, I-35128 Padova, Italy;4. Department of Information Engineering, University of Padova, I-35121 Padova, Italy;1. Consejo Nacional de Ciencia y Tecnología (CONACYT)-Laboratorio de Genómica del Metabolismo Óseo, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico;2. Laboratorio de Genómica del Metabolismo Óseo, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico;3. Laboratorio de Genética, Dirección de Investigación, Instituto Nacional de Rehabilitación, Mexico City, Mexico;4. Centro de Investigación en Políticas, Población y Salud, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico;5. Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico;6. Unidad de Investigación Epidemiológica y en Servicios de Salud, Instituto Mexicano del Seguro Social (IMSS), Cuernavaca, Morelos, Mexico;7. Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico |
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| Abstract: | Cervical cancer is a critically malignant tumor with the second mortality of females worldwide. MicroRNAs (miRNAs) are short but regulatory non-coding RNAs playing a pivotal role in many biological processes including tumorigenesis. However, the exact role of miR-140-3p in cervical cancer remains to be elucidated. Here we identified that miR-140-3p was significantly reduced in cervical cancer tissues by comprehensive analysis of TCGA data, hinting that higher expression level of miR-140-3p predicted a good clinical prognosis. Quantitative real-time PCR (RT-qPCR) assay was performed to confirm the negative correlation between miR-140-3p expression level and human cervical cancer tissues as well as various cervical cancer cell lines. To clarify the certain role of miR-140-3p, forced expression by microRNA mimics was applied in Caski and C33A cells, showing that miR-140-3p overexpression significantly impeded the proliferation of cervical cancer cells by cell count kit (CCK-8) assay. Western blot analysis of cell cycle-related proteins Cyclin A, Cyclin B1 and Cyclin D1 have further confirmed the cell cycle arrest was induced by the ectopic expression of miR-140-3p. Annexin-V based FACS analysis also found the simultaneous appearance of early apoptotic cell population in miR-140-3p overexpression cells. The protein level of BCL-2 was attenuated in accompany with elevated Bax and Cleaved caspase-3 protein, indicating miR-140-3p overexpression induced early apoptosis. Mechanistically, we demonstrated that miR-140-3p could target the 3′UTR of RRM2 which has been proved to be highly involved in the onset of cancer. Furthermore, upregulation of miR-140-3p and RRM2 failed to inhibit the proliferation of human cervical cancer cells, revealing that RRM2 served as the target downstream gene of miR-140-3p abolishing its ability as a tumor suppressor. Overall, we figured out the new role of miR-140-3p in cervical cancer and concluded that miR-140-3p was a candidate of cancer control in preclinical. |
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| Keywords: | Cervical cancer miR-140-3p RRM2 |
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