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JMJD2A facilitates growth and inhibits apoptosis of cervical cancer cells by downregulating tumor suppressor miR?491?5p.

ABSTRACT: Cervical cancer remains the second most common malignancy for women worldwide. Jumonji domain containing 2A (JMJD2A), a member of the JmjC domain?containing family of JMJD2 proteins, is capable of regulating cancer?associated genes, including genes involved in the cell cycle, proliferation, apoptosis, invasion and metastasis. However, its role in human cervical cancer has yet to be elucidated. microRNA (miR)?491?5p, a mature form of miR?491, has been shown to function as a tumor suppressor gene in vitro by inducing apoptosis and inhibiting proliferation and invasion in various types of cancer. However, the underlying mechanism remains to be elucidated. In the present study it was observed that JMJD2A expression was significantly upregulated in human cervical cancer cell lines and cervical epithelial carcinoma tissues. A high JMJD2A level predicted poor overall and disease?free survival rate and may serve as an independent prognostic factor for adverse outcome. JMJD2A increased cervical cancer cell and colony numbers in vitro, increased the tumor weight in a mouse xenograft model, and decreased the apoptotic rate by downregulating the pro?apoptotic proteins Bax, p21 and active caspase?3, and upregulating the anti?apoptotic protein Bcl?2. Transfection experiments indicated that the role of JMJD2A in cervical cancer was mediated, at least in part, by the repression of miR?491?5p. In summary, JMJD2A was identified as an oncogenic protein in human cervical cancer that significantly affected cell and colony numbers, tumor weight and apoptosis via the downregulation of miR?491?5p, which acts as a tumor suppressor in cervical cancer. Therefore, JMJD2A may serve as a prognostic factor and potential target for intervention in cervical cancer.

SUBMITTER: Li Y

PROVIDER: S-EPMC6423651 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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JMJD2A facilitates growth and inhibits apoptosis of cervical cancer cells by downregulating tumor suppressor miR‑491‑5p.

Li Yan Y Wang Ya'ning Y Xie Zhen Z Hu Hongyi H

Molecular medicine reports 20190131 4

Cervical cancer remains the second most common malignancy for women worldwide. Jumonji domain containing 2A (JMJD2A), a member of the JmjC domain‑containing family of JMJD2 proteins, is capable of regulating cancer‑associated genes, including genes involved in the cell cycle, proliferation, apoptosis, invasion and metastasis. However, its role in human cervical cancer has yet to be elucidated. microRNA (miR)‑491‑5p, a mature form of miR‑491, has been shown to function as a tumor suppressor gene ...[more]

PMID: 30720092

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Project description:MicroRNA-491-5p (miR-491-5p) plays an important role in regulating cell proliferation and migration; however, the effect of miR-491-5p on neovascularization after traumatic brain injury remains poorly understood. In this study, a controlled cortical injury model in C57BL/6 mice and an oxygen-glucose deprivation model in microvascular endothelial cells derived from mouse brain were established to simulate traumatic brain injury in vivo and in vitro, respectively. In the in vivo model, quantitative real-time-polymerase chain reaction results showed that the expression of miR-491-5p increased or decreased following the intracerebroventricular injection of an miR-491-5p agomir or antagomir, respectively, and the expression of miR-491-5p decreased slightly after traumatic brain injury. To detect the neuroprotective effects of miR-491-p, neurological severity scores, Morris water maze test, laser speckle techniques, and immunofluorescence staining were assessed, and the results revealed that miR-491-5p downregulation alleviated neurological dysfunction, promoted the recovery of regional cerebral blood flow, increased the number of lectin-stained microvessels, and increased the survival of neurons after traumatic brain injury. During the in vitro experiments, the potential mechanism of miR-491-5p on neovascularization was explored through quantitative real-time-polymerase chain reaction, which showed that miR-491-5p expression increased or decreased in brain microvascular endothelial cells after transfection with an miR-491-5p mimic or inhibitor, respectively. Dual-luciferase reporter and western blot assays verified that metallothionein-2 was a target gene for miR-491-5p. Cell counting kit 8 (CCK-8) assay, flow cytometry, and 2?,7?-dichlorofluorescein diacetate (DCFH-DA) assay results confirmed that the downregulation of miR-491-5p increased brain microvascular endothelial cell viability, reduced cell apoptosis, and alleviated oxidative stress under oxygen-glucose deprivation conditions. Cell scratch assay, Transwell assay, tube formation assay, and western blot assay results demonstrated that miR-491-5p downregulation promoted the migration, proliferation, and tube formation of brain microvascular endothelial cells through a metallothionein-2-dependent hypoxia-inducible factor-1α/vascular endothelial growth factor pathway. These findings confirmed that miR-491-5p downregulation promotes neovascularization, restores cerebral blood flow, and improves the recovery of neurological function after traumatic brain injury. The mechanism may be mediated through a metallothionein-2-dependent hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway and the alleviation of oxidative stress. All procedures were approved by Ethics Committee of the First Affiliated Hospital of Chongqing Medical University, China (approval No. 2020-304) on June 22, 2020.

Dataset Information

JMJD2A facilitates growth and inhibits apoptosis of cervical cancer cells by downregulating tumor suppressor miR?491?5p.

Publications

JMJD2A facilitates growth and inhibits apoptosis of cervical cancer cells by downregulating tumor suppressor miR‑491‑5p.

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