Myosin Heavy Chain-Associated RNA Transcripts Promotes Gastric Cancer Progression Through the miR-4529-5p/ROCK2 Axis

被引:5
作者
Sun, Xiaoli [1 ]
Zhang, Xinwu [1 ]
Chen, Shuo [1 ]
Fan, Meng [1 ]
Ma, Shuangyu [1 ]
Zhai, Hongjun [1 ]
机构
[1] Xi An Jiao Tong Univ, Dept Gen Surg, Affiliated Hosp 2, 157 Xinwu Rd, Xian 710004, Shaanxi, Peoples R China
关键词
LncRNA; MHRT; Gastric cancer; hsa-miR-4529-5p; ROCK2; LONG NONCODING RNAS; RHO-KINASE; HEPATOCELLULAR-CARCINOMA; TUMOR-GROWTH; ROCK2; ACTIVATION; APOPTOSIS; PROTECTS; ROLES; HEART;
D O I
10.1007/s10620-019-05708-1
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background and AimCharacterization of genetic aberrations provides novel strategies for diagnosis and treatment of gastric cancer. Accumulating evidence has shown the involvement of long non-coding RNA (lncRNA) in the pathology of gastric cancer, especially in proliferation and metastasis. The aim of this study was to delineate the role of myosin heavy chain-associated RNA transcripts (MHRT), a heart-specific lncRNA, in gastric cancer and to understand the correlation between MHRT, miR-4529-5p, and ROCK2.MethodsTo study expression level of MHRT, clinical gastric cancer samples, gastric cancer cell lines, adjacent normal tissues, and gastric epithelial cell lines were used. Additionally, apoptosis, proliferation, and invasion of gastric cancer cells were studied with or without downregulation of MHRT and miR-4529-5p.ResultsWe identified that MHRT was ectopically expressed in gastric cancer tissues and cell lines. Interestingly, similar to the anti-apoptotic role of MHRT in cardiomyocytes, our data illustrated that MHRT inhibits apoptosis of gastric cancer cells. Moreover, we found that MHRT promotes proliferation and invasion of gastric cancer cells in vitro. Importantly, our data revealed that MHRT regulates the expression of miR-4529-5p via direct binding. Additionally, functional experiments illustrated that miR-4529-5p is particularly responsible for MHRT-mediated regulation of apoptosis. Besides, ROCK2 was identified as a downstream target of miR-4529-5p. Additionally, upregulated MHRT promotes the expression of ROCK2 by inhibiting miR-4529-5p.ConclusionOur data illustrated a MHRT/miR-4529-5p/ROCK2 regulatory axis that contributes to the tumorigenesis of gastric cancer and provided potential therapeutic targets for precise gastric cancer treatment.
引用
收藏
页码:3539 / 3548
页数:10
相关论文
共 35 条
[1]   The Rho-kinase inhibitor HA-1077 suppresses proliferation/migration and induces apoptosis of urothelial cancer cells [J].
Abe, Hideyuki ;
Kamai, Takao ;
Hayashi, Keitaro ;
Anzai, Naohiko ;
Shirataki, Hiromichi ;
Mizuno, Tomoya ;
Yamaguchi, Yoshiyuki ;
Masuda, Akinori ;
Yuki, Hideo ;
Betsunoh, Hironori ;
Yashi, Masahiro ;
Fukabori, Yoshitatsu ;
Yoshida, Ken-Ichiro .
BMC CANCER, 2014, 14
[2]   Bcl-3 regulates TGFβ signaling by stabilizing Smad3 during breast cancer pulmonary metastasis [J].
Chen, Xi ;
Cao, Xinwei ;
Sun, Xiaohua ;
Lei, Rong ;
Chen, Pengfei ;
Zhao, Yongxu ;
Jiang, Yuhang ;
Yin, Jie ;
Chen, Ran ;
Ye, Deji ;
Wang, Qi ;
Liu, Zhanjie ;
Liu, Sanhong ;
Cheng, Chunyan ;
Mao, Jie ;
Hou, Yingyong ;
Wang, Mingliang ;
Siebenlist, Ulrich ;
Chin, Y. Eugene ;
Wang, Ying ;
Cao, Liu ;
Hu, Guohong ;
Zhang, Xiaoren .
CELL DEATH & DISEASE, 2016, 7 :e2508-e2508
[3]   Profiling and targeting of cellular mitochondrial bioenergetics: inhibition of human gastric cancer cell growth by carnosine [J].
Cheng, Jiao-yan ;
Yang, Jian-bo ;
Liu, Yuan ;
Xu, Min ;
Huang, Yu-yan ;
Zhang, Jing-jing ;
Cao, Pei ;
Lyu, Jian-xin ;
Shen, Yao .
ACTA PHARMACOLOGICA SINICA, 2019, 40 (07) :938-948
[4]   The cross talk between long, non-coding RNAs and microRNAs in gastric cancer [J].
Deng, Kaiyuan ;
Wang, Hao ;
Guo, Xiaoqiang ;
Xia, Jiazeng .
ACTA BIOCHIMICA ET BIOPHYSICA SINICA, 2016, 48 (02) :111-116
[5]   An integrated encyclopedia of DNA elements in the human genome [J].
Dunham, Ian ;
Kundaje, Anshul ;
Aldred, Shelley F. ;
Collins, Patrick J. ;
Davis, CarrieA. ;
Doyle, Francis ;
Epstein, Charles B. ;
Frietze, Seth ;
Harrow, Jennifer ;
Kaul, Rajinder ;
Khatun, Jainab ;
Lajoie, Bryan R. ;
Landt, Stephen G. ;
Lee, Bum-Kyu ;
Pauli, Florencia ;
Rosenbloom, Kate R. ;
Sabo, Peter ;
Safi, Alexias ;
Sanyal, Amartya ;
Shoresh, Noam ;
Simon, Jeremy M. ;
Song, Lingyun ;
Trinklein, Nathan D. ;
Altshuler, Robert C. ;
Birney, Ewan ;
Brown, James B. ;
Cheng, Chao ;
Djebali, Sarah ;
Dong, Xianjun ;
Dunham, Ian ;
Ernst, Jason ;
Furey, Terrence S. ;
Gerstein, Mark ;
Giardine, Belinda ;
Greven, Melissa ;
Hardison, Ross C. ;
Harris, Robert S. ;
Herrero, Javier ;
Hoffman, Michael M. ;
Iyer, Sowmya ;
Kellis, Manolis ;
Khatun, Jainab ;
Kheradpour, Pouya ;
Kundaje, Anshul ;
Lassmann, Timo ;
Li, Qunhua ;
Lin, Xinying ;
Marinov, Georgi K. ;
Merkel, Angelika ;
Mortazavi, Ali .
NATURE, 2012, 489 (7414) :57-74
[6]   Emerging Roles for Natural MicroRNA Sponges [J].
Ebert, Margaret S. ;
Sharp, Phillip A. .
CURRENT BIOLOGY, 2010, 20 (19) :R858-R861
[7]   Rho-Kinase inhibitor fasudil suppresses high glucose-induced H9c2 cell apoptosis through activation of autophagy [J].
Gao, Huikuan ;
Hou, Fei ;
Dong, Ruiqing ;
Wang, Zefeng ;
Zhao, Can ;
Tang, Wurina ;
Wu, Yongquan .
CARDIOVASCULAR THERAPEUTICS, 2016, 34 (05) :352-359
[8]   Identification of aberrantly expressed long non-coding RNAs in stomach adenocarcinoma [J].
Gu, Jianbin ;
Li, Yong ;
Fan, Liqiao ;
Zhao, Qun ;
Tan, Bibo ;
Hua, Kelei ;
Wu, Guobin .
ONCOTARGET, 2017, 8 (30) :49201-49216
[9]   Modular regulatory principles of large non-coding RNAs [J].
Guttman, Mitchell ;
Rinn, John L. .
NATURE, 2012, 482 (7385) :339-346
[10]   A long noncoding RNA protects the heart from pathological hypertrophy [J].
Han, Pei ;
Li, Wei ;
Lin, Chiou-Hong ;
Yang, Jin ;
Shang, Ching ;
Nurnberg, Sylvia T. ;
Jin, Kevin Kai ;
Xu, Weihong ;
Lin, Chieh-Yu ;
Lin, Chien-Jung ;
Xiong, Yiqin ;
Chien, Huan-Chieh ;
Zhou, Bin ;
Ashley, Euan ;
Bernstein, Daniel ;
Chen, Peng-Sheng ;
Chen, Huei-Sheng Vincent ;
Quertermous, Thomas ;
Chang, Ching-Pin .
NATURE, 2014, 514 (7520) :102-+