Liang Gehao, Liu Zihao, Tan Luyuan, Su A N, Jiang Wen G, Gong Chang
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetic and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, P.R. China.
Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff University, Cardiff, U.K.
Anticancer Res. 2017 Aug;37(8):4337-4343. doi: 10.21873/anticanres.11827.
Accumulating evidence has shown that hypoxia plays a key role in regulating proliferation of breast cancer cells. However, the mechanism of how hypoxia regulates breast cancer remains unclear. We sought to investigate if hypoxia regulated proliferation through circular RNA.
Western blot was used to detect hypoxia-inducible factor 1 alpha (HIF1α) levels in breast cancer cells under hypoxic conditions. Candidate circular RNAs (circRNAs) were selected and quantified by quantitative real-time polymerase chain reaction (qRT-PCR) after hypoxia induction. CCK8 assay was used to investigate the changes of proliferation after interfering circDENND4C and HIF1a.
In breast cancer cells, circDENND4C was increased under hypoxic conditions and decreased after knocking-down HIF1α. In addition, knocking-down circDENND4C inhibited proliferation of breast cancer cells in a hypoxic environment. Finally, tumors with a large size had higher circDENND4C expression levels than those of small size.
CircDENND4C is a HIF1α-associated circRNA promoting the proliferation of breast cancer cells under hypoxia.
越来越多的证据表明,缺氧在调节乳腺癌细胞增殖中起关键作用。然而,缺氧如何调节乳腺癌的机制仍不清楚。我们试图研究缺氧是否通过环状RNA调节增殖。
采用蛋白质免疫印迹法检测缺氧条件下乳腺癌细胞中缺氧诱导因子1α(HIF1α)水平。缺氧诱导后,通过定量实时聚合酶链反应(qRT-PCR)筛选并定量候选环状RNA(circRNA)。使用CCK8法研究干扰circDENND4C和HIF1α后增殖的变化。
在乳腺癌细胞中,缺氧条件下circDENND4C增加,敲低HIF1α后减少。此外,敲低circDENND4C可抑制缺氧环境中乳腺癌细胞的增殖。最后,大尺寸肿瘤的circDENND4C表达水平高于小尺寸肿瘤。
CircDENND4C是一种与HIF1α相关的circRNA,在缺氧条件下促进乳腺癌细胞的增殖。