Yang Lin, Bi Lei, Liu Qingwei, Zhao Meng, Cao Bin, Li Dong, Xiu Jianjun
Department of Radiology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
Department of Radiology, Affiliated Hospital of Qingdao University Medical College, Qingdao 266003, China.
Dis Markers. 2015;2015:383056. doi: 10.1155/2015/383056. Epub 2015 Aug 18.
Hiwi is well known for its role in stem cell renewal, maintaining the resting stage, and downregulating cell cycle of stem cells via RNA silencing. And Hiwi overexpression has been recognized in several types of cancers. In the present study, we examined the Hiwi expression in colorectal cancer (CRC) specimens in both mRNA and protein levels via real-time quantitative PCR, western blot assay, and immunohistochemical staining. Then we explored the role of Hiwi in the cancer cell proliferation and in the DNA methylation in human CRC Caro-2 and HT-29 cell lines. Results demonstrated that both mRNA and protein levels of Hiwi were significantly higher in 38 CRC tissues than in 38 peritumor tissues. Moreover, the Hiwi overexpression with an adenovirus vector significantly promoted the proliferation of Caro-2 and HT-29 cells, associated with significant increase in the global DNA methylation levels. And the chemical inhibition of DNA methylation significantly restrained such proliferation promotion. In summary, we confirmed that Hiwi was overexpressed in CRC tissues and that the forced Hiwi overexpression promoted the proliferation and global DNA methylation of CRC cell lines. Our results imply for the first time that Hiwi promotes the proliferation of CRC cells via promoting global DNA methylation.
Hiwi因其在干细胞更新、维持静止期以及通过RNA沉默下调干细胞细胞周期中的作用而闻名。并且Hiwi的过表达已在几种类型的癌症中被识别。在本研究中,我们通过实时定量PCR、蛋白质印迹分析和免疫组织化学染色,在mRNA和蛋白质水平上检测了结直肠癌(CRC)标本中Hiwi的表达。然后我们探讨了Hiwi在人CRC Caro-2和HT-29细胞系中癌细胞增殖和DNA甲基化中的作用。结果表明,38例CRC组织中Hiwi的mRNA和蛋白质水平均显著高于38例癌旁组织。此外,用腺病毒载体过表达Hiwi显著促进了Caro-2和HT-29细胞的增殖,同时伴随着整体DNA甲基化水平的显著增加。而DNA甲基化化学抑制显著抑制了这种增殖促进作用。总之,我们证实Hiwi在CRC组织中过表达,并且强制过表达Hiwi促进了CRC细胞系的增殖和整体DNA甲基化。我们的结果首次表明,Hiwi通过促进整体DNA甲基化来促进CRC细胞的增殖。