Xiaohong Zhao, Lichun Fan, Na Xie, Kejian Zou, Xiaolan Xiao, Shaosheng Wang
Maternal and Child Health Hospital of Hainan Province, 15th South of Longkun Road, Haikou, Hainan Province, 570206, People's Republic of China.
Department of Pathology, The Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, 571101, China.
Tumour Biol. 2016 Nov;37(11):14989-14997. doi: 10.1007/s13277-016-5415-1. Epub 2016 Sep 21.
MicroRNAs (miRNAs) play an important role in the tumorigenesis of ovarian cancer. Previously, we have reported the dysregulation of miR-203 in the ovarian cancer tissues. However, the biological functions and molecular mechanisms of miR-203 in ovarian cancer remain unknown. Here, we showed that the expression of miR-203 was increased in ovarian cancer tissues compared with the adjacent non-cancerous tissues and the transcription of miR-203 was inhibited by P53. Forced expression of miR-203 in ovarian cancer promoted cell growth and migration, while depletion of miR-203 inhibited the growth and migration of ovarian cancer cells. In addition, miR-203 promoted the metastasis of ovarian cancer cells in vivo and shorted the survival of the nude mice. Mechanically, miR-203 targeted the 3'-UTR of pyruvate dehydrogenase B (PDHB) and increased the consumption of glucose and the production of lactate. Overexpression of PDHB abolished the oncogenic effects of miR-203 on the growth of ovarian cancer cells. Together, our data suggested the oncogenic roles of miR-203 in ovarian cancer by promoting glycolysis, and miR-203 might be a therapeutic target for ovarian cancer.
微小RNA(miRNA)在卵巢癌的肿瘤发生过程中发挥着重要作用。此前,我们已报道过卵巢癌组织中miR-203的表达失调。然而,miR-203在卵巢癌中的生物学功能和分子机制仍不清楚。在此,我们发现与相邻的非癌组织相比,miR-203在卵巢癌组织中的表达增加,且miR-203的转录受到P53的抑制。在卵巢癌中强制表达miR-203可促进细胞生长和迁移,而敲低miR-203则抑制卵巢癌细胞的生长和迁移。此外,miR-203可促进卵巢癌细胞在体内的转移,并缩短裸鼠的生存期。机制上,miR-203靶向丙酮酸脱氢酶B(PDHB)的3'-非翻译区,增加葡萄糖消耗和乳酸生成。过表达PDHB可消除miR-203对卵巢癌细胞生长的致癌作用。总之,我们的数据表明miR-203通过促进糖酵解在卵巢癌中发挥致癌作用,且miR-203可能是卵巢癌的一个治疗靶点。