Zhou Jiaojiao, Zhang Mengwen, Huang Yanqing, Feng Lin, Chen Hailong, Hu Yiwang, Chen Huarong, Zhang Kaitai, Zheng Lei, Zheng Shu
Department of Surgical Oncology, the Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang 310009, China; The Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, 88 Jie-Fang Rd, Hangzhou, Zhejiang 310009, China.
State Key Laboratory of Molecular Oncology, Cancer Institute & Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 10021, China; Department of Etiology and Carcinogenesis, Cancer Institute & Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 10021, China; Cancer Institute & Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 10021, China.
Cancer Lett. 2015 Jan 28;356(2 Pt B):669-75. doi: 10.1016/j.canlet.2014.10.014. Epub 2014 Oct 16.
Colorectal cancer metastasis is believed to be associated with microRNA dysregulation. However, little is known as to how microRNAs regulate colorectal cancer proliferation, invasion and metastasis. In the present study, we compared the microRNA expression profiles between patients of colorectal cancer at diagnosis with and without liver metastasis. MicroRNA-320b was found to be among those up-regulated in the patient group with metastasis. We subsequently found that microRNA-320b, opposite of its homolog, microRNA-320a that differs by only a single nucleotide, functions in promoting colorectal cancer cell proliferation and invasion. Moreover, we found that overexpression of exogenous microRNA-320b can up-regulate the target genes of microRNA-320a including β-catenin, Neuropilin-1 and Rac-1, which are all known to promote tumor proliferation, invasion and metastasis. These results suggest that microRNA-320b may function in competing with microRNA-320a. Thus, our study has proposed one novel mechanism for controlling colorectal cancer proliferation and invasion through homologous competition between microRNAs. This mechanism may be important for colorectal cancer metastasis.
结直肠癌转移被认为与微小RNA失调有关。然而,关于微小RNA如何调节结直肠癌的增殖、侵袭和转移,我们知之甚少。在本研究中,我们比较了诊断时伴有和不伴有肝转移的结直肠癌患者之间的微小RNA表达谱。发现微小RNA-320b在伴有转移的患者组中上调。随后我们发现,微小RNA-320b与其仅相差一个核苷酸的同源物微小RNA-320a相反,具有促进结直肠癌细胞增殖和侵袭的作用。此外,我们发现外源性微小RNA-320b的过表达可上调微小RNA-320a的靶基因,包括β-连环蛋白、神经纤毛蛋白-1和Rac-1,这些基因均已知可促进肿瘤增殖、侵袭和转移。这些结果表明,微小RNA-320b可能与微小RNA-320a相互竞争发挥作用。因此,我们的研究提出了一种通过微小RNA之间的同源竞争来控制结直肠癌增殖和侵袭的新机制。该机制可能对结直肠癌转移具有重要意义。