LncRNA HOXA-AS2 Facilitates Tumorigenesis and Progression of Papillary Thyroid Cancer by Modulating the miR-15a-5p/HOXA3 Axis

被引：63
作者：
Jiang, Liangfeng [1 ]
Wu, Zhiming [2 ]
Meng, Xingcheng [2 ]
Chu, Xiufeng [2 ]
Huang, Hongjun [2 ]
Xu, Chaoyang [3 ]
机构：
[1] First Peoples Hosp Fuyang Hangzhou, Pharm Dept, Hangzhou, Zhejiang, Peoples R China
[2] China Med Univ, Shaoxing Hosp, Gen Surg Dept, 1 Huayu Rd, Shaoxing 312030, Peoples R China
[3] Peoples Hosp Shaoxing, Dept Thyroid Breast Surg, Shaoxing, Peoples R China
来源：
HUMAN GENE THERAPY | 2019年 / 30卷 / 05期
关键词：
HOXA-AS2; miR-15a-5p; HOXA3; Wnt; beta-catenin signaling pathway; papillary thyroid cancer; NONCODING RNA TUG1; CELL-PROLIFERATION; HEPATOCELLULAR-CARCINOMA; PROMOTES TUMORIGENESIS; MESENCHYMAL TRANSITION; C-MYC; EXPRESSION; CERNA; METASTASIS; PROGNOSIS;
D O I：
10.1089/hum.2018.109
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
The long non-coding RNA HOXA-AS2 has been found to be an oncogene in several types of human malignant tumors. However, its role in regulating the occurrence and development of papillary thyroid cancer (PTC) is still unclear. The present study investigated the function and mechanism(s) of HOXA-AS2 in PTC progression. Using quantitative real-time polymerase chain reaction, HOXA-AS2 was found to be differentially expressed in PTC tissues and cell lines. Kaplan-Meier analysis indicated that the overall survival rate of patients with higher levels of HOXA-AS2 was lower than those with relatively lower levels. Loss-of-function assays revealed that HOXA-AS2 knockdown inhibited PTC progression by inhibiting cellular proliferation, migration, and invasion and accelerating apoptosis. Mechanistically, loss-of-function assays showed a positive correlation between HOXA3 and HOXA-AS2 expression. Subcellular fractionation assay results revealed abundant HOXA-AS2 expression in the cytoplasm of PTC cells. Additionally, FOXD2-AS1 was found to upregulate HOXA3 expression by binding to miR-15a-5p. Finally, rescue assays demonstrated the overall function of the HOXA-AS2/miR-15a-5p/HOXA3 axis in PTC progression. These findings will significantly contribute to further research and the development of more efficient treatments for thyroid cancer in the future.
引用
收藏
页码：618 / 631
页数：14
相关论文
共 51 条
[1]   Integrated Genomic Characterization of Papillary Thyroid Carcinoma [J].
Agrawal, Nishant ;
Akbani, Rehan ;
Aksoy, B. Arman ;
Ally, Adrian ;
Arachchi, Harindra ;
Asa, Sylvia L. ;
Auman, J. Todd ;
Balasundaram, Miruna ;
Balu, Saianand ;
Baylin, Stephen B. ;
Behera, Madhusmita ;
Bernard, Brady ;
Beroukhim, Rameen ;
Bishop, Justin A. ;
Black, Aaron D. ;
Bodenheimer, Tom ;
Boice, Lori ;
Bootwalla, Moiz S. ;
Bowen, Jay ;
Bowlby, Reanne ;
Bristow, Christopher A. ;
Brookens, Robin ;
Brooks, Denise ;
Bryant, Robert ;
Buda, Elizabeth ;
Butterfield, Yaron S. N. ;
Carling, Tobias ;
Carlsen, Rebecca ;
Carter, Scott L. ;
Carty, Sally E. ;
Chan, Timothy A. ;
Chen, Amy Y. ;
Cherniack, Andrew D. ;
Cheung, Dorothy ;
Chin, Lynda ;
Cho, Juok ;
Chu, Andy ;
Chuah, Eric ;
Cibulskis, Kristian ;
Ciriello, Giovanni ;
Clarke, Amanda ;
Clayman, Gary L. ;
Cope, Leslie ;
Copland, John A. ;
Covington, Kyle ;
Danilova, Ludmila ;
Davidsen, Tanja ;
Demchok, John A. ;
DiCara, Daniel ;
Dhalla, Noreen .
CELL, 2014, 159 (03) :676-690
[2]   Analysis of long non-coding RNA expression profiles in gastric cancer [J].
Cao, Wei-Jun ;
Wu, Hai-Lu ;
He, Bang-Shun ;
Zhang, Yu-Shu ;
Zhang, Zhen-Yu .
WORLD JOURNAL OF GASTROENTEROLOGY, 2013, 19 (23) :3658-3664
[3]   Long non-coding RNA UICLM promotes colorectal cancer liver metastasis by acting as a ceRNA for microRNA-215 to regulate ZEB2 expression [J].
Chen, Dong-liang ;
Lu, Yun-xin ;
Zhang, Jia-xing ;
Wei, Xiao-li ;
Wang, Feng ;
Zeng, Zhao-lei ;
Pan, Zhi-zhong ;
Yuan, Yun-fei ;
Wang, Feng-hua ;
Pelicano, Helene ;
Chiao, Paul J. ;
Huang, Peng ;
Xie, Dan ;
Li, Yu-hong ;
Ju, Huai-qiang ;
Xu, Rui-hua .
THERANOSTICS, 2017, 7 (19) :4836-4849
[4]   Cancer Statistics in China, 2015 [J].
Chen, Wanqing ;
Zheng, Rongshou ;
Baade, Peter D. ;
Zhang, Siwei ;
Zeng, Hongmei ;
Bray, Freddie ;
Jemal, Ahmedin ;
Yu, Xue Qin ;
He, Jie .
CA-A CANCER JOURNAL FOR CLINICIANS, 2016, 66 (02) :115-132
[5]   Long Noncoding RNA LINC01234 Functions as a Competing Endogenous RNA to Regulate CBFB Expression by Sponging miR-204-5p in Gastric Cancer [J].
Chen, Xin ;
Chen, Zhenyao ;
Yu, Shanxun ;
Nie, Fengqi ;
Yan, Shuai ;
Ma, Pei ;
Chen, Qinnan ;
Wei, Chenchen ;
Fu, Hangjiang ;
Xu, Tianwei ;
Ren, Shengnan ;
Sun, Ming ;
Wang, Zhaoxia .
CLINICAL CANCER RESEARCH, 2018, 24 (08) :2002-2014
[6]   LncRNA H19/miR-29b-3p/PGRN Axis Promoted Epithelial-Mesenchymal Transition of Colorectal Cancer Cells by Acting on Wnt Signaling [J].
Ding, Dayong ;
Li, Changfeng ;
Zhao, Tiancheng ;
Li, Dandan ;
Yang, Lei ;
Zhang, Bin .
MOLECULES AND CELLS, 2018, 41 (05) :423-435
[7]   Long noncoding RNA HOXA-AS2 represses P21 and KLF2 expression transcription by binding with EZH2, LSD1 in colorectal cancer [J].
Ding, J. ;
Xie, M. ;
Lian, Y. ;
Zhu, Y. ;
Peng, P. ;
Wang, J. ;
Wang, L. ;
Wang, K. .
ONCOGENESIS, 2017, 6 :e288-e288
[8]   Expression of hepaCAM inhibits bladder cancer cell proliferation via a Wnt/-catenin-dependent pathway in vitro and in vivo [J].
Du, Hong-fei ;
Ou, Li-ping ;
Lv, Chang-kun ;
Yang, Xue ;
Song, Xue-dong ;
Fan, Yan-ru ;
Wu, Xiao-hou ;
Luo, Chun-li .
CANCER BIOLOGY & THERAPY, 2015, 16 (10) :1502-1513
[9]   LncRNA n335586/miR-924/CKMT1A axis contributes to cell migration and invasion in hepatocellular carcinoma cells [J].
Fan, Hongxia ;
Lv, Ping ;
Mu, Ting ;
Zhao, Xiaopei ;
Liu, Yankun ;
Feng, Yujie ;
Lv, Jing ;
Liu, Min ;
Tang, Hua .
CANCER LETTERS, 2018, 429 :89-99
[10]   RETRACTED: Long Non-Coding RNA HOXA-AS2 Regulates Malignant Glioma Behaviors and Vasculogenic Mimicry Formation via the MiR-373/EGFR Axis (Retracted article. See vol. 57, pg. 410, 2023) [J].
Gao, Yana ;
Yu, Hai ;
Liu, Yunhui ;
Liu, Xiaobai ;
Zheng, Jian ;
Ma, Jun ;
Gong, Wei ;
Chen, Jiajia ;
Zhao, Lini ;
Tian, Yu ;
Xue, Yixue .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2018, 45 (01) :131-147
123456