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长链非编码 RNA KB-1471A8.2 过表达抑制卵巢癌细胞增殖和迁移并拮抗紫杉醇耐药性。

LncRNA KB-1471A8.2 Overexpression Suppresses Cell Proliferation and Migration and Antagonizes the Paclitaxel Resistance of Ovarian Cancer Cells.

机构信息

1 Department of Gynecology, Women's Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing, China.

2 Department of Gynecology, Jiangyin Maternity and Child Health Care Hospital, Jiangyin, China.

出版信息

Cancer Biother Radiopharm. 2019 Jun;34(5):316-324. doi: 10.1089/cbr.2018.2698. Epub 2019 Mar 20.

DOI:10.1089/cbr.2018.2698
PMID:30892073
Abstract

The aim was to investigate the lncRNA KB-1471A8.2 function in ovarian cancer progression and paclitaxel resistance. The expression and distribution of KB-1471A8.2 was detected by qRT-PCR. The cell proliferation, apoptosis, invasion, migration and chemoresistance were analyzed by CCK8 assay, flow cytometry and transwell assay. The expression of DEPTOR, whose sequence is reverse overlapped with KB-1471A8.2 was analyzed by qRT-PCR, western blot and immunofluorescence. The cell cycle and the cell cycle related gene expression were analyzed by flow cytometry and qRT-PCR, respectively. KB-1471A8.2 was significantly downregulated in both ovarian cancer tissues and chemoresistant ovarian cancer cells. Overexpression of KB-1471A8.2 significantly inhibited the proliferation, invasion, migration, and paclitaxel resistance, and increased the apoptosis of ovarian cancer cells. KB-1471A8.2 was mainly distributed in the nucleus of ovarian cancer cells. KB-1471A8.2 overexpression significantly decreased the S phase cell ratio, increased the G0/G1 phase cell ratio, but not affected the expression and distribution of DEPTOR. However, cyclin-dependent kinase 4 (), which is an important regulator of G1/S transition, was significantly decreased in KB-1471A8.2-overexpressed ovarian cancer cells. KB-1471A8.2 could significantly inhibit the development and paclitaxel resistance of ovarian cancer cells, at least partly, by suppressing expression.

摘要

目的在于研究长链非编码 RNA KB-1471A8.2 在卵巢癌进展和紫杉醇耐药中的作用。通过 qRT-PCR 检测 KB-1471A8.2 的表达和分布。通过 CCK8 检测、流式细胞术和 Transwell 检测分析细胞增殖、凋亡、侵袭、迁移和化疗耐药性。通过 qRT-PCR、western blot 和免疫荧光分析与 KB-1471A8.2 序列反向重叠的 DEPTOR 的表达。通过流式细胞术和 qRT-PCR 分别分析细胞周期和细胞周期相关基因的表达。KB-1471A8.2 在卵巢癌组织和耐药性卵巢癌细胞中均显著下调。KB-1471A8.2 的过表达显著抑制卵巢癌细胞的增殖、侵袭、迁移和紫杉醇耐药性,并增加其凋亡。KB-1471A8.2 主要分布在卵巢癌细胞的核内。KB-1471A8.2 的过表达显著降低 S 期细胞比例,增加 G0/G1 期细胞比例,但不影响 DEPTOR 的表达和分布。然而,细胞周期蛋白依赖性激酶 4(),作为 G1/S 过渡的重要调节因子,在 KB-1471A8.2 过表达的卵巢癌细胞中显著降低。KB-1471A8.2 可通过抑制表达,显著抑制卵巢癌细胞的发展和紫杉醇耐药性,至少部分如此。

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