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Journal of cellular physiology v.233 no.10, 2018년, pp.6578 - 6588  

MicroRNA‐497 accelerates apoptosis while inhibiting proliferation, migration, and invasion through negative regulation of the MAPK/ERK signaling pathway via RAF‐1

Tao, Ling (The 4th Department of Gynecological Surgery, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, P.R. China ) ; Zhang, Chun‐Yu (The 4th Department of Gynecological Surgery, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, P.R. China ) ; Guo, Lei (The 4th Department of Gynecological Surgery, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, P.R. China ) ; Li, Xia (The 4th Department of Gynecological Surgery, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, P.R. China ) ; Han, Na‐Na (The 4th Department of Gynecological Surgery, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, P.R. China ) ; Zhou, Qi (Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, P.R. China ) ; Liu, Zhi‐Le ;
  • 초록  

    The aim of this study is to explore the various modes of action miR‐497 has on human cervical cancer (CC) cell behavior. We also speculate that miR‐497 achieves its anti‐tumor role by governing RAF‐1 via MAPK/ERK signaling pathway. CC tissues with corresponding adjacent normal tissues were collected from 168 CC patients. RAF‐1 ‐ positive cells were identified by means of immunohistochemistry in tissues. A series of inhibitors, mimics and siRNA against RAF‐1 were introduced to validate regulatory mechanisms for miR‐497 and RAF‐1. Quantitative real‐time polymerase chain reaction (qRT‐PCR) and Western blot assay were employed for evaluating alternations of miR‐497, RAF‐1, and MAPK/ERK signaling pathway. HeLa cell proliferation, invasion, migration, cycle progression, and apoptosis were assessed by means of CCK‐8, wound‐healing, transwell invasion assays, and flow cytometry, respectively. The target prediction program and luciferase activity determination were used to identify miR‐497 targeting RAF‐1. We determined reduced miR‐497 expression and elevated expression of RAF‐1 in CC tissues as opposed to adjacent tissues. Transfection of miR‐497 mimics and siRNA‐RAF‐1 both decreased levels of MEK1, ERK1, and p38 phosphorylation in HeLa cells, inhibited cell proliferation, migration and invasion, induced more cells arrested in the G0/G1 phase, and promoted cell apoptosis; while miR‐497 inhibitors led to opposite results. These findings indicate miR‐497 as a tumor suppressor results from negative regulation of the MAPK/ERK signaling pathway via RAF‐1 in CC.


  • 주제어

    apoptosis .   cervical cancer .   extracellular .   microRNA‐497 .   migration .   RAF‐1.  

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