Zhou Yanqing, Xu Xiaying, Lv Huabing, Wen Qirong, Li Juan, Tan Linyu, Li Jianqi, Sheng Xiujie
Department of Obstetrics and Gynecology, The Third Affiliated Hospital and Key laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institute in Guangdong Province, Guangzhou Medical University, Guangzhou, China.
PLoS One. 2016 May 26;11(5):e0155250. doi: 10.1371/journal.pone.0155250. eCollection 2016.
Metastasis associated in lung adenocarcinoma transcript-1 (MALAT-1) is overexpressed during cancer progression and promotes cell migration and invasion in many solid tumors. However, its role in ovarian cancer remains poorly understood.
Expressions of MALAT-1 were detected in 37 normal ovarian tissues and 45 ovarian cancer tissues by reverse transcription polymerase chain reaction (RT-PCR). Cell proliferation was observed by CCK-8 assay; Flow cytometry was used to measure cell cycle and apoptosis; Cell migration was detected by transwell migration and invasion assay. In order to evaluate the function of MALAT-1, shRNA combined with DNA microarray and Functional enrichment analysis were performed to determine the transcriptional effects of MALAT-1 silencing in OVCAR3 cells. RNA and protein expression were measured by qRT-PCR and Western blotting, respectively.
We found that upregulation of MALAT-1 mRNA in ovarian cancer tissues and enhanced MALAT-1 expression was associated with FIGO stage. Knockdown of MALAT-1 expression in OVCAR3 cells inhibited cell proliferation, migration, and invasion, leading to G0/G1 cell cycle arrest and apoptosis. Overexpressed MALAT-1 expression in SKOV3 cells promoted cell proliferation, migration and invasion. Downregulation of MALAT-1 resulted in significant change of gene expression (at least 2-fold) in 449 genes, which regulate proliferation, cell cycle, and adhesion. As a consequence of MALAT-1 knockdown, MMP13 protein expression decreased, while the expression of MMP19 and ADAMTS1 was increased.
The present study found that MALAT-1 is highly expressed in ovarian tumors. MALAT-1 promotes the growth and migration of ovarian cancer cells, suggesting that MALAT-1 may be an important contributor to ovarian cancer development.
肺癌腺癌转移相关转录本1（MALAT-1）在癌症进展过程中过度表达，并促进许多实体瘤中的细胞迁移和侵袭。然而，其在卵巢癌中的作用仍知之甚少。
通过逆转录聚合酶链反应（RT-PCR）检测37例正常卵巢组织和45例卵巢癌组织中MALAT-1的表达。采用CCK-8法观察细胞增殖；流式细胞术用于检测细胞周期和凋亡；通过Transwell迁移和侵袭试验检测细胞迁移。为了评估MALAT-1的功能，进行了shRNA结合DNA微阵列和功能富集分析，以确定MALAT-1沉默对OVCAR3细胞的转录影响。分别通过qRT-PCR和蛋白质印迹法检测RNA和蛋白质表达。
我们发现卵巢癌组织中MALAT-1 mRNA上调，且MALAT-1表达增强与国际妇产科联盟（FIGO）分期相关。敲低OVCAR3细胞中MALAT-1的表达可抑制细胞增殖迁移和侵袭，导致细胞周期停滞于G0/G1期并诱导凋亡。在SKOV3细胞中过表达MALAT-1可促进细胞增殖、迁移和侵袭。MALAT-1的下调导致449个调节增殖、细胞周期和黏附的基因表达发生显著变化（至少2倍）。MALAT-1敲低的结果是，基质金属蛋白酶13（MMP13）蛋白表达降低，而MMP19和含血小板反应蛋白基序的解聚素样金属蛋白酶1（ADAMTS1）的表达增加。
本研究发现MALAT-1在卵巢肿瘤中高表达。MALAT-1促进卵巢癌细胞的生长和迁移，提示MALAT-1可能是卵巢癌发生发展的重要因素。
