Sun Qian, Li Qian, Xie Fangfang
Department of Obstetrics and Gynecology, The 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou, Gansu 730050, People's Republic of China.
Onco Targets Ther. 2019 Aug 9;12:6297-6307. doi: 10.2147/OTT.S214689. eCollection 2019.
Ovarian cancer (OC) is a common female disease with a poor prognosis. But the possible mechanism of OC tumor progression remains an active area of research. This study is intended to explore the effect of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on proliferation and apoptosis of OC and its mechanism.
MALAT1 and miR-503-5p expressions in human OC cell lines and normal human ovarian epithelial (HOSE) cell line were measured using qRT-PCR. OC cell line SKOV3 is divided into 4 groups: pcDNA3.1 group, pcDNA3.1-MALAT1 group, si-NC group, and si-MALAT1 group. MTT assay and 5-ethynyl-2'-deoxyuridine (EdU) assay were applied for the detection of cell proliferation. Relationship of MALAT1 with miR-503-5p was verified using luciferase assay and RNA pull-down. The luciferase activity in cells was normalized to RNA concentrations determined by Bradford assays.
MALAT1 expression in OC cells was elevated compared with HOSE cells. MTT assay and EdU assay supported that si-MALAT1 could inhibit cell proliferation in OC cells. Treatment of si-MALAT1 results in increased cell apoptosis rate in both SKOV3 cells and OVCAR3 cells. The expression of lncRNA-MALAT1 was negatively associated with the expression of miR-503-5p in OC cells, while luciferase assay and RNA pull-down together supported the direct binding of MALAT1 with miR-503-5p. Knockdown of MALAT1 was able to inhibit the activation of JAK2/STAT3 signal pathway, and MALAT1 overexpression was accompanied by activation of these factors.
lncRNA-MALAT1 can negatively target miR-503-5p expression to further promote proliferation and depress apoptosis of OC cells through the JAK2-STAT3 pathway.
卵巢癌（OC）是一种常见的女性疾病，预后较差。但OC肿瘤进展的可能机制仍是一个活跃的研究领域。本研究旨在探讨转移相关肺腺癌转录本1（MALAT1）对OC细胞增殖和凋亡的影响及其机制。
采用qRT-PCR检测人OC细胞系和正常人卵巢上皮（HOSE）细胞系中MALAT1和miR-503-5p的表达。将OC细胞系SKOV3分为4组：pcDNA3.1组、pcDNA3.1-MALAT1组、si-NC组和si-MALAT1组。采用MTT法和5-乙炔基-2'-脱氧尿苷（EdU）法检测细胞增殖。通过荧光素酶报告基因检测和RNA下拉实验验证MALAT1与miR-503-5p的关系。细胞中的荧光素酶活性通过Bradford法测定的RNA浓度进行标准化。
与HOSE细胞相比，OC细胞中MALAT1表达升高。MTT法和EdU法均表明si-MALAT1可抑制OC细胞的增殖。si-MALAT1处理导致SKOV3细胞和OVCAR3细胞的凋亡率增加。lncRNA-MALAT1的表达与OC细胞中miR-503-5p的表达呈负相关，而荧光素酶报告基因检测和RNA下拉实验共同支持MALAT1与miR-503-5p直接结合。敲低MALAT1能够抑制JAK2/STAT3信号通路的激活，而MALAT1过表达则伴随着这些因子的激活。
lncRNA-MALAT1可通过JAK2-STAT3途径负向靶向miR-503-5p的表达，进而促进OC细胞的增殖并抑制其凋亡。
