Ning Zhifeng, Zhang Youzhi, Chen Hanwei, Wu Jiliang, Song Tieshan, Wu Qian, Liu Fuxing
Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning 437100, China ; The Basic Medical School, Hubei University of Science and Technology, Xianning 437100, China.
School of Pharmacy, Hubei University of Science and Technology, Xianning 437100, China.
Oxid Med Cell Longev. 2014;2014:193523. doi: 10.1155/2014/193523. Epub 2014 May 22.
Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), a coregulator of estrogen receptors alpha and beta, is a potential protooncogene implicated in several human cancers, including sexual hormone-responsive or sexual hormone-nonresponsive cancers. However, the functions of PELP1 in colorectal cancer remain unclear. In this study, western blot and bioinformatics revealed that PELP1 expression was higher in several colorectal cancer cell lines than in immortalized normal colorectal epithelium. PELP1 silencing by short hairpin RNA promoted the senescence and inhibited the proliferation, colony formation, migration, invasion, and xenograft tumor formation of the CRC cell line HT-29. Moreover, PELP1 silencing was accompanied by c-Src downregulation. c-Src upregulation partly alleviated the damage in HT-29 malignant behavior induced by PELP1 RNA interference. In conclusion, PELP1 exhibits an oncogenic function in colorectal cancer through c-Src upregulation.
富含脯氨酸、谷氨酸和亮氨酸的蛋白1(PELP1)是雌激素受体α和β的一种共调节因子,是一种潜在的原癌基因,与包括性激素反应性或性激素非反应性癌症在内的多种人类癌症有关。然而,PELP1在结直肠癌中的功能仍不清楚。在本研究中,蛋白质印迹法和生物信息学显示,几种结直肠癌细胞系中PELP1的表达高于永生化正常结直肠上皮细胞。短发夹RNA介导的PELP1沉默促进了CRC细胞系HT-29的衰老,并抑制了其增殖、集落形成、迁移、侵袭和异种移植瘤形成。此外,PELP1沉默伴随着c-Src的下调。c-Src上调部分缓解了PELP1 RNA干扰诱导的HT-29恶性行为损伤。总之,PELP1通过上调c-Src在结直肠癌中发挥致癌作用。