miR-1246 Targets CCNG2 to Enhance Cancer Stemness and Chemoresistance in Oral Carcinomas

被引:69
作者
Lin, Shih-Shen [1 ,2 ]
Peng, Chih-Yu [1 ,2 ]
Liao, Yi-Wen [1 ]
Chou, Ming-Yung [1 ,2 ,3 ]
Hsieh, Pei-Ling [4 ]
Yu, Cheng-Chia [1 ,2 ,3 ]
机构
[1] Chung Shan Med Univ, Sch Dent, Taichung 40201, Taiwan
[2] Chung Shan Med Univ Hosp, Dept Dent, Taichung 40201, Taiwan
[3] Chung Shan Med Univ, Inst Oral Sci, Taichung 40201, Taiwan
[4] China Med Univ, Sch Med, Dept Anat, Taichung 40402, Taiwan
关键词
oral squamous cell carcinomas; miR-1246; cancer stemness; chemoresistance; CCNG2; SQUAMOUS-CELL CARCINOMA; CYCLIN G2; MESENCHYMAL TRANSITION; MICRORNA EXPRESSION; PANCREATIC-CANCER; TUMOR-GROWTH; LUNG-CANCER; HEAD; PROMOTES; MARKER;
D O I
10.3390/cancers10080272
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
MiRNAs have been recognized as crucial components in carcinogenesis, but whether miR-1246 affects the cancer sternness and drug resistance in oral squamous cell carcinoma (OSCC) has not been fully understood and its downstream targets still need to be unraveled. In the present work, we employed miRNAs RT-PCR analysis to evaluate the expression of miR-1246 in tumor tissues and oral cancer stem cells (OCSC). Stemness phenotypes, including self-renewal, migration, invasion, colony formation capacities, and in vivo oncogenicity of oral cancer cells following transfected with miR-1246 inhibitors or mimics were examined. Our results suggested that the expression level of miR-1246 was significantly upregulated in the tumor tissues and OCSC. Kaplan-Meier survival analysis of OSCC patients with high levels of miR-1246 had the worst survival rate compared to their low-expression counterparts. Inhibition of miR-1246 in OCSC significantly reduced the stemness hallmarks, while overexpression of miR-1246 enhanced these characteristics. Moreover, we showed that downregulation of miR-1246 decreased chemoresistance. In addition, we verified that miR-1246-inhibited CCNG2 contributed to the cancer stemness of OSCC. These results demonstrated the significance of miR-1246 in the regulation of OSCC stemness. Targeting miR-1246-CCNG2 axis may be beneficial to suppress cancer relapse and metastasis in OSCC patients.
引用
收藏
页数:14
相关论文
共 51 条
[1]  
Balz V, 2003, CANCER RES, V63, P1188
[2]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[3]   Cyclin G2 inhibits epithelial-to-mesenchymal transition by disrupting Wnt/β-catenin signaling [J].
Bernaudo, S. ;
Salem, M. ;
Qi, X. ;
Zhou, W. ;
Zhang, C. ;
Yang, W. ;
Rosman, D. ;
Deng, Z. ;
Ye, G. ;
Yang, B. B. ;
Vanderhyden, B. ;
Wu, Z. ;
Peng, C. .
ONCOGENE, 2016, 35 (36) :4816-4827
[4]   miRNA-1246 induces pro-inflammatory responses in mesenchymal stem/stromal cells by regulating PKA and PP2A [J].
Bott, Alexander ;
Erdem, Nese ;
Lerrer, Shalom ;
Hotz-Wagenblatt, Agnes ;
Breunig, Christian ;
Abnaof, Khalid ;
Woerner, Angelika ;
Wilhelm, Heike ;
Muenstermann, Ewald ;
Ben-Baruch, Adit ;
Wiemann, Stefan .
ONCOTARGET, 2017, 8 (27) :43897-43914
[5]   Octamer 4/MicroRNA-1246 Signaling Axis Drives Wnt/β-Catenin Activation in Liver Cancer Stem Cells [J].
Chai, Stella ;
Ng, Kai-Yu ;
Tong, Man ;
Lau, Eunice Y. ;
Lee, Terence K. ;
Chan, Kwok Wah ;
Yuan, Yun-Fei ;
Cheung, Tan-To ;
Cheung, Siu-Tim ;
Wang, Xiao-Qi ;
Wong, Nathalie ;
Lo, Chung-Mau ;
Man, Kwan ;
Guan, Xin-Yuan ;
Ma, Stephanie .
HEPATOLOGY, 2016, 64 (06) :2062-2076
[6]   Activation of microRNA-494-targeting Bmi1 and ADAM10 by silibinin ablates cancer stemness and predicts favourable prognostic value in head and neck squamous cell carcinomas [J].
Chang, Yu-Chao ;
Jan, Chia-Ing ;
Peng, Chih-Yu ;
Lai, Yu-Chi ;
Hu, Fang-Wei ;
Yu, Cheng-Chia .
ONCOTARGET, 2015, 6 (27) :24002-24016
[7]   Changes in the expression of cyclin G2 in esophageal cancer cell and its significance [J].
Chen, J. Q. ;
Liu, C. J. ;
Wen, H. X. ;
Shi, C. L. ;
Zhang, H. S. ;
Li, M. ;
Sun, G. G. .
TUMOR BIOLOGY, 2014, 35 (04) :3355-3362
[8]   Nonadhesive Culture System as a Model of Rapid Sphere Formation with Cancer Stem Cell Properties [J].
Chen, Su-Feng ;
Chang, Yun-Ching ;
Nieh, Shin ;
Liu, Chia-Lin ;
Yang, Chin-Yuh ;
Lin, Yaoh-Shiang .
PLOS ONE, 2012, 7 (02)
[9]   Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma [J].
Chiou, Shih-Hwa ;
Yu, Cheng-Chia ;
Huang, Chi-Yang ;
Lin, Shu-Chun ;
Liu, Chung-Ji ;
Tsai, Tung-Hu ;
Chou, Shiu-Huey ;
Chien, Chian-Shiu ;
Ku, Hung-Hai ;
Lo, Jeng-Fan .
CLINICAL CANCER RESEARCH, 2008, 14 (13) :4085-4095
[10]   Sox2 expression involvement in the oncogenicity and radiochemoresistance of oral cancer stem cells [J].
Chou, Ming-Yung ;
Hu, Fang-Wei ;
Yu, Chuan-Hang ;
Yu, Cheng-Chia .
ORAL ONCOLOGY, 2015, 51 (01) :31-39