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长链非编码 RNA 反义非编码 RNA 在 INK4 基因座的下调抑制了 Wnt/β-catenin 诱导的 OVCAR-3 细胞增殖和凋亡。

Down-regulation of long non-coding RNA antisense non-coding RNA in the INK4 locus suppresses OVCAR-3 cells proliferation and induction of apoptosis by Wnt/β-catenin.

机构信息

Department of Gynecology, Maternal and Child Health Care Hospital of Shandong Province, Jinan City, Shandong Province,China.

Department of Obstetrics and Gynecology, Huantai County People's Hospital, Zibo City, Shandong Province,China.

出版信息

J Pharm Pharmacol. 2021 Aug 12;73(9):1212-1217. doi: 10.1093/jpp/rgab042.

Abstract

OBJECTIVES

Ovarian cancer is a lethal gynecological malignancy. Long non-coding RNA antisense non-coding RNA in the INK4 locus (lncRNA ANRIL) was reported to have a critical role in cancer advancement. The ANRIL-mediated oncogenic underlying molecular mechanisms are not fully understood in ovarian cancer. We aimed to study ANRIL silencing effects on the proliferation and apoptosis of OVCAR-3 cells.

METHODS

The ANRIL was Knockdown by transfection of OVCAR-3 cells with si-RNA against ANRIL. MTT assay and cell death ELISA kit were used to evaluate cellular proliferation and apoptosis. The expression levels of ANRIL, pro-and anti-apoptotic genes were assessed using q-RT-PCR. Western blotting was used to assess Wnt/β-catenin signalling pathway.

KEY FINDINGS

ANRIL down-regulating in OVCAR-3 cell lines resulted in significant inhibition of cellular proliferation, apoptosis induction, as well as suppression of cellular invasion. Besides, knockdown of ANRIL led to pro-apoptotic genes up-regulation, Bad and Bax and anti-apoptotic genes down-regulation, Bid and Bcl-2. More importantly, we observed that ANRIL inhibition suppressed the vital components expression of the Wnt/β-catenin cascade.

CONCLUSION

Our findings showed that down-regulation of lncRNA ANRIL resulted in the effective suppression of OVCAR-3 cell proliferation and invasion and induction of apoptosis by preventing Wnt/β-catenin signal transduction.

摘要

目的

卵巢癌是一种致命的妇科恶性肿瘤。长链非编码 RNA 反义非编码 RNA 在 INK4 基因座(lncRNA ANRIL)被报道在癌症进展中具有关键作用。在卵巢癌中,ANRIL 介导的致癌潜在分子机制尚不完全清楚。我们旨在研究沉默 ANRIL 对 OVCAR-3 细胞增殖和凋亡的影响。

方法

通过转染针对 ANRIL 的 siRNA 沉默 OVCAR-3 细胞中的 ANRIL。MTT 法和细胞死亡 ELISA 试剂盒用于评估细胞增殖和凋亡。使用 q-RT-PCR 评估 ANRIL、促凋亡和抗凋亡基因的表达水平。Western blot 用于评估 Wnt/β-catenin 信号通路。

主要发现

在 OVCAR-3 细胞系中下调 ANRIL 导致细胞增殖显著抑制、凋亡诱导以及细胞侵袭抑制。此外,敲低 ANRIL 导致促凋亡基因上调,Bad 和 Bax,以及抗凋亡基因下调,Bid 和 Bcl-2。更重要的是,我们观察到 ANRIL 抑制抑制了 Wnt/β-catenin 级联的重要组成部分的表达。

结论

我们的研究结果表明,下调长链非编码 RNA ANRIL 通过阻止 Wnt/β-catenin 信号转导,有效抑制了 OVCAR-3 细胞的增殖和侵袭,并诱导了凋亡。

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