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miRNA-338-3p 通过 MAPK 信号通路靶向调控 MACC1 抑制宫颈癌的增殖。

MiRNA-338-3p regulates cervical cancer cells proliferation by targeting MACC1 through MAPK signaling pathway.

机构信息

Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.

出版信息

Eur Rev Med Pharmacol Sci. 2017 Dec;21(23):5342-5352. doi: 10.26355/eurrev_201712_13919.

Abstract

OBJECTIVE

Aberrant expression of miR-338-3p has recently involved in the progression and development of various types of malignant tumors, but its role in the progression of cervical cancer remains unknown. This study aims to investigate the role of miR-338-3p/MACC1 axis in the progression of cervical cancer.

PATIENTS AND METHODS

MiR-338-3p and metastasis-associated in colon cancer 1 (MACC1) expression was determined in cervical cancer by quantitative real-time PCR (qRT-PCR). We explored the association of miR-338-3p expression with pathology and prognosis in cervical cancer patients. We explored the function of miR-338-3p and MACC1 on cell proliferation. A luciferase reporter assay was conducted to confirm the target gene of miR-338-3p in cervical cancer cells.

RESULTS

In the present work, our data showed that the expression of miR-338-3p was substantially decreased in cervical cancer tissues and associated with advanced FIGO stage, lymph node metastasis, depth of cervical invasion and poor overall survival. However, the MACC1 had an opposite expression. Mechanistically, we identified that MACC1 which acted as a functional downstream target for miR-338-3p. Furthermore, overexpression of miR-338-3p decreased expression of MACC1 in cervical cancer cells could significantly inhibit cervical cancer cell proliferation and induce cells apoptosis. Interestingly, miR-338-3p and MACC1 had proven to be involved in the progression of cervical cancer cells by regulating mitogen-activated protein kinase (MAPK) signaling pathway.

CONCLUSIONS

Our results suggested miR-338-3p/MACC1/MAPK regulatory pathway play an important role in the progression of cervical cancer.

摘要

目的

miR-338-3p 的异常表达最近涉及多种恶性肿瘤的进展和发展,但它在宫颈癌进展中的作用尚不清楚。本研究旨在探讨 miR-338-3p/MACC1 轴在宫颈癌进展中的作用。

患者和方法

通过定量实时 PCR(qRT-PCR)测定宫颈癌中 miR-338-3p 和结肠癌转移相关基因 1(MACC1)的表达。我们探讨了 miR-338-3p 表达与宫颈癌患者病理和预后的关系。我们探讨了 miR-338-3p 和 MACC1 对细胞增殖的功能。通过荧光素酶报告基因检测证实了 miR-338-3p 在宫颈癌细胞中的靶基因。

结果

在本工作中,我们的数据表明 miR-338-3p 的表达在宫颈癌组织中显著降低,并与 FIGO 晚期分期、淋巴结转移、宫颈浸润深度和不良总生存相关。然而,MACC1 的表达则相反。机制上,我们确定 MACC1 是 miR-338-3p 的功能性下游靶基因。此外,miR-338-3p 的过表达降低了宫颈癌细胞中 MACC1 的表达,可显著抑制宫颈癌细胞增殖并诱导细胞凋亡。有趣的是,miR-338-3p 和 MACC1 通过调节丝裂原活化蛋白激酶(MAPK)信号通路被证明参与了宫颈癌的进展。

结论

我们的研究结果表明,miR-338-3p/MACC1/MAPK 调控通路在宫颈癌的进展中起着重要作用。

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