MicroRNA-130b functions as a tumor suppressor by regulating RUNX3 in epithelial ovarian cancer

被引:19
|
作者
Paudel, Dhruba [1 ]
Zhou, Wei [1 ]
Ouyang, Yiqin [1 ]
Dong, Shengnan [1 ]
Huang, Qingting [1 ]
Giri, Ranjana [1 ]
Wang, Jianjun [1 ]
Tong, Xiaowen [1 ]
机构
[1] Tongji Univ, Sch Med, Shanghai Tongji Hosp, Dept Gynecol & Obstet, Shanghai 200092, Peoples R China
关键词
Epithelial ovarian cancer; MicroRNA-130b; Runt domain transcription factor; Clinicopathological feature; Migration; Invasion; ONCOGENIC ROLE; MIR-130B; RESISTANCE; PROTEIN; EXPRESSION; PROMOTES; TARGETS;
D O I
10.1016/j.gene.2016.04.001
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Aim: To evaluate the clinical significance of microRNA (miR)-130b-Runt domain transcription factor (RUNX3) axis and its effects on oncogenic phenotypes of human epithelial ovarian cancer (EOC). Methods: QRT-PCR was performed to detect the expression of miR-130b and RUNX3 mRNA in 100 EOC and 20 normal ovarian tissues. The associations between miR-130b and/or RUNX3 expression and various clinicopathological features of EOC patients were statistically analyzed. Then, the effects of miR-130b-RUNX3 axis on migration and invasion of EOC cells were assessed in vitro. Results: miR-130b expression was downregulated, while RUNX3 mRNA was upregulated, in EOC tissues compared to normal ovarian tissues (both P = 0.001). Importantly, the expression level of miR-130b in EOC tissues was negatively correlated with that of RUNX3 mRNA significantly. Additionally, miR-130b-low and/or RUNX3-high expression were all closely correlated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage (all P < 0.05). Moreover, overexpression of miR-130b reduced the expression of RUNX3 and inhibited cancer cell migration and invasion of EOC cells, whereas knockdown of miR-130b increased the expression of RUNX3 and promoted cancer cell migration and invasion of EOC cells. After that, the impaired motility of the miR-130b overexpression cells was recovered partly by the expression of RUNX3. Furthermore, the knockdown of RUNX3 also gave rise to a decrease in cell migration and invasion. Conclusion: Our data reveal that the dysregulation of miR-130b-RUNX3 axis may play important roles in EOC development and progression, and the loss of miR-130b may contribute to the malignant biological behavior of EOC cells via regulating the expression of RUNX3, implying their potentials as promising markers for predicting EOC progression and as candidate targets for gene therapy. (C) 2016 Elsevier B.V. All rights reserved.
引用
收藏
页码:48 / 55
页数:8
相关论文
共 50 条
  • [1] MicroRNA-130b regulates the tumour suppressor RUNX3 in gastric cancer
    Lai, Kin Wai
    Koh, King Xin
    Loh, Marie
    Tada, Kotaro
    Subramaniam, Manish Mani
    Lim, Xn Yii
    Vaithilingam, Aparna
    Salto-Tellez, Manuel
    Iacopetta, Barry
    Ito, Yoshiaki
    Soong, Richie
    EUROPEAN JOURNAL OF CANCER, 2010, 46 (08) : 1456 - 1463
  • [2] MicroRNA-130b is a candidate epigenetic regulator of the gastric tumor suppressor RUNX3
    Lai, Kin Wai
    Koh, King Xin
    Chuang, Linda
    Voon, Dominic
    Loh, Marie
    Wu, Mengchu
    Tada, Kotaro
    Salto-Tellez, Manuel
    Ito, Yoshiaki
    Soong, Richie
    CANCER RESEARCH, 2009, 69
  • [3] RUNX3 functions as an oncogene in ovarian cancer
    Lee, Cecilia Wei Lin
    Chuang, Linda Shyue Huey
    Kimura, Shunichi
    Lai, Soak Kuan
    Ong, Chee Wee
    Yan, Benedict
    Salto-Tellez, Manuel
    Choolani, Mahesh
    Ito, Yoshiaki
    GYNECOLOGIC ONCOLOGY, 2011, 122 (02) : 410 - 417
  • [4] Tumor suppressor function of RUNX3 in breast cancer
    Chen, Lin-Feng
    JOURNAL OF CELLULAR BIOCHEMISTRY, 2012, 113 (05) : 1470 - 1477
  • [5] RUNX3 is a Tumor Suppressor in Human Pancreatic Cancer
    Jain, M.
    Baine, M. J.
    Senapati, S.
    Batra, S. K.
    PANCREAS, 2011, 40 (08) : 1328 - 1329
  • [6] Tumor suppressor activity of RUNX3
    Bae, SC
    Choi, JK
    ONCOGENE, 2004, 23 (24) : 4336 - 4340
  • [7] Tumor suppressor activity of RUNX3
    Suk-Chul Bae
    Joong-Kook Choi
    Oncogene, 2004, 23 : 4336 - 4340
  • [8] MicroRNA-106b regulates the tumor suppressor RUNX3 in laryngeal carcinoma cells
    Xu, Ying
    Wang, Kai
    Gao, Wei
    Zhang, Chunming
    Huang, Fuhui
    Wen, Shuxin
    Wang, Binquan
    FEBS LETTERS, 2013, 587 (19): : 3166 - 3174
  • [9] RUNX3 protein is overexpressed in human epithelial ovarian cancer
    Nevadunsky, Nicole S.
    Barbieri, John S.
    Kwong, Joseph
    Merritt, Melissa A.
    Welch, William R.
    Berkowitz, Ross S.
    Mok, Samuel C.
    GYNECOLOGIC ONCOLOGY, 2009, 112 (02) : 325 - 330
  • [10] RUNX3 contributes to carboplatin resistance in epithelial ovarian cancer cells
    Barghout, Samir H.
    Zepeda, Nubia
    Vincent, Krista
    Azad, Abul K.
    Xu, Zhihua
    Yang, Christine
    Steed, Helen
    Postovit, Lynne-Marie
    Fu, YangXin
    GYNECOLOGIC ONCOLOGY, 2015, 138 (03) : 647 - 655