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长链非编码 RNA MALAT1 在卵巢癌组织中上调,并促进 SK-OV-3 细胞增殖和侵袭。

Long non-coding RNA MALAT1 is up-regulated in ovarian cancer tissue and promotes SK-OV-3 cell proliferation and invasion.

出版信息

Neoplasma. 2016;63(6):865-872. doi: 10.4149/neo_2016_605.

Abstract

Ovarian cancer is a gynecological malignancy worldwide. Long non-coding RNAs (lncRNAs) research is an emerging area in cancer studies, but little is known about lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in ovarian cancer. This study aims to investigate expression and roles of MALAT1 in ovarian cancer. MALAT1 level was detected in 20 ovarian cancer patients. MALAT1 expression was promoted by transforming growth factor β1 (TGFB1) treatment and inhibited by siRNA transfection in human ovarian cancer cell line SK-OV-3, after which changes in cell viability, proliferation, migration and invasion were analyzed by MTT, colony formation and Transwell assays. Protein levels of mitogen-activated protein kinase factors, including MAPK kinase 1 (MEK1), extracellular signal-regulated kinase (ERK1), p38 and c-Jun N-terminal kinase 1 (JNK1), were detected by western blot. Results showed that MALAT1 was significantly up-regulated in ovarian cancer tissues compared to adjacent normal tissues (P < 0.001), and its expression was correlated to tumor size (r2 = 0.7770, P < 0.0001) and metastasis. TGFB1 and siRNA successfully altered MALAT1 levels in SK-OV-3 cells. Knockdown of MALAT1 suppressed SK-OV-3 cell viability, proliferation, migration and invasion (P < 0.05), and inhibited phosphorylation of MEK1, ERK1, p38 and JNK1, which suggested that MALAT1 promoted ovarian cancer cell proliferation, migration and invasion, and that MAPK pathways might be one of the regulatory mechanisms of MALAT1. This study reveals that MALAT1 is a potential biomarker for tumor growth and metastasis, as well as a promising therapeutic target in ovarian cancer, facilitating further ovarian cancer research.

摘要

卵巢癌是一种全球性的妇科恶性肿瘤。长链非编码 RNA(lncRNA)的研究是癌症研究中的一个新兴领域,但关于卵巢癌中 lncRNA 转移相关肺腺癌转录本 1(MALAT1)的了解甚少。本研究旨在探讨 MALAT1 在卵巢癌中的表达和作用。检测了 20 例卵巢癌患者的 MALAT1 水平。转化生长因子β1(TGFB1)处理可促进 MALAT1 的表达,人卵巢癌细胞系 SK-OV-3 中的 siRNA 转染可抑制 MALAT1 的表达,然后通过 MTT、集落形成和 Transwell 测定分析细胞活力、增殖、迁移和侵袭的变化。通过 Western blot 检测丝裂原活化蛋白激酶因子,包括丝裂原活化蛋白激酶激酶 1(MEK1)、细胞外信号调节激酶 1(ERK1)、p38 和 c-Jun N-末端激酶 1(JNK1)的蛋白水平。结果表明,与相邻正常组织相比,卵巢癌组织中 MALAT1 显著上调(P<0.001),其表达与肿瘤大小(r2=0.7770,P<0.0001)和转移相关。TGFB1 和 siRNA 成功改变了 SK-OV-3 细胞中的 MALAT1 水平。敲低 MALAT1 抑制 SK-OV-3 细胞活力、增殖、迁移和侵袭(P<0.05),并抑制 MEK1、ERK1、p38 和 JNK1 的磷酸化,这表明 MALAT1 促进卵巢癌细胞增殖、迁移和侵袭,MAPK 途径可能是 MALAT1 的调节机制之一。本研究揭示 MALAT1 是肿瘤生长和转移的潜在生物标志物,也是卵巢癌有前途的治疗靶点,为进一步研究卵巢癌提供了便利。

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