Shi Rong, Zhou Jue-Yu, Zhou Hui, Zhao Zhen, Liang Sang-Hua, Zheng Wen-Ling, Ma Wen-Li
Institute of Genetic Engineering, Southern Medical University, Guangzhou 510515, China.
Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China.
Biomed Res Int. 2014;2014:978984. doi: 10.1155/2014/978984. Epub 2014 Feb 3.
As a major tumor suppressor gene, the role of PinX1 in breast cancer and its molecular mechanism remain unclear. In this study, overexpression of PinX1 was generated in 3 breast cancer cell lines, and knockdown of PinX1 was performed in a nontumorigenic breast cell line. The regulation of PinX1 on cell proliferation and cell cycle was observed. A microarray-based lncRNA and mRNA expression profile screening was also performed. We found a lower growth rate, G0/G1 phase arrest, and S phase inhibition in the PinX1 overexpressed breast cancer cells, while a higher growth rate, decreased G0/G1 phase, and increased S phase rate in the PinX1 knocked-down nontumorigenic breast cell. A total of 977 mRNAs and 631 lncRNAs were identified as differentially expressed transcripts between PinX1 overexpressed and control MCF-7 cells. Further analysis identified the involvement of these mRNAs in 52 cancer related pathways and various other biological processes. 11 enhancer-like lncRNAs and 25 lincRNAs with their adjacent mRNA pairs were identified as coregulated transcripts. Our results confirmed the role of PinX1 as a major tumor suppressor gene in breast cancer cell lines and provided information for further research on the molecular mechanisms of PinX1 in tumorigenesis.
作为一种主要的肿瘤抑制基因，PinX1在乳腺癌中的作用及其分子机制仍不清楚。在本研究中，在3种乳腺癌细胞系中实现了PinX1的过表达，并在一种非致瘤性乳腺细胞系中进行了PinX1的敲低。观察了PinX1对细胞增殖和细胞周期的调控。还进行了基于微阵列的lncRNA和mRNA表达谱筛选。我们发现PinX1过表达的乳腺癌细胞生长速率降低，出现G0/G1期阻滞和S期抑制，而PinX1敲低的非致瘤性乳腺细胞生长速率升高，G0/G1期减少，S期速率增加。在PinX1过表达的MCF-7细胞和对照细胞之间，共鉴定出977个mRNA和631个lncRNA作为差异表达转录本。进一步分析确定这些mRNA参与了52条癌症相关通路和各种其他生物学过程。11个增强子样lncRNA和25个与其相邻mRNA对的lincRNA被鉴定为共调控转录本。我们的结果证实了PinX1作为乳腺癌细胞系中主要肿瘤抑制基因的作用，并为进一步研究PinX1在肿瘤发生中的分子机制提供了信息。
