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Inhibition of the long non-coding RNA MALAT1 suppresses tumorigenicity and induces apoptosis in the human ovarian cancer SKOV3 cell line

机译:抑制长非编码RNA MALAT1可抑制人卵巢癌SKOV3细胞株的致瘤性并诱导细胞凋亡

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摘要

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a 8,000 nucleotide-long, spliced non-coding RNA, which has been reported to be deregulated in several tumors. However, to the best of our knowledge, the role of MALAT1 in ovarian cancer has not been previously investigated. The aim of the present study was to investigate the effect of MALAT1 inhibition on the tumorigenity of SKOV3 cells. First, stable MALAT1-knockdown ovarian cancer cells and control cells were established using lentivirus-mediated artificial micro RNA interference in order to investigate the effect of MALAT1 inhibition on cell viability, clonability, migration, invasion and apoptosis in vitro. In addition, the effect of MALAT1 on cell growth in nude mice was assessed. To identify the possible targets of MALAT1, total RNA was extracted from MALAT1-knockdown cells and control cells and a microarray analysis was performed. The results showed that MALAT1 inhibition significantly suppressed tumorigenity in vitro and in vivo (P<0.01). Compared with the control cells, 921 genes in the MALAT1-knockdown cells were deregulated by at least two-fold. The results of the reverse transcription-quantitative polymerase chain reaction showed that 19 of the 20 genes selected for validation confirmed the deregulation indicated by the microarray analysis. The findings define a major oncogenic role for MALAT1, which may offer an attractive novel target for therapeutic intervention in ovarian cancer.
机译:转移相关的肺腺癌转录本1(MALAT1)是8,000个核苷酸长的剪接非编码RNA,据报道在几种肿瘤中该RNA失控。然而,就我们所知,MALAT1在卵巢癌中的作用尚未得到过研究。本研究的目的是研究MALAT1抑制对SKOV3细胞致瘤性的影响。首先,使用慢病毒介导的人工微RNA干扰建立稳定的MALAT1基因敲除卵巢癌细胞和对照细胞,以研究MALAT1抑制作用对体外细胞活力,克隆性,迁移,侵袭和凋亡的影响。此外,评估了MALAT1对裸鼠细胞生长的影响。为了鉴定MALAT1的可能靶标,从MALAT1敲低细胞和对照细胞中提取总RNA,并进行了微阵列分析。结果表明,MALAT1抑制作用在体内外均显着抑制了致癌性(P <0.01)。与对照细胞相比,MALAT1敲低细胞中的921个基因被至少降低了两倍。逆转录定量聚合酶链反应的结果表明,选择用于验证的20个基因中的19个证实了微阵列分析表明的失调。这些发现定义了MALAT1的主要致癌作用,这可能为卵巢癌的治疗干预提供有吸引力的新靶标。

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