Circular RNA hsa_circRNA_102209 promotes the growth and metastasis of colorectal cancer through miR-761-mediated Ras and Rab interactor 1 signaling

被引:41
作者
Li, Chi [1 ]
Zhou, Hong [2 ]
机构
[1] Jinzhou Med Univ, Dept Gen Surg, Affiliated Hosp 1, Jinzhou, Peoples R China
[2] Jinzhou Med Univ, Affiliated Hosp 1, Radiol, Jinzhou, Peoples R China
关键词
colorectal cancer; growth; hsa_circRNA_102209; metastasis; RIN1; signaling; HEPATOCELLULAR-CARCINOMA; APOPTOSIS; GENES;
D O I
10.1002/cam4.3332
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In our study, has_circRNA_102209 was the most elevated regulator in colorectal cancer (CRC) tissues according to circRNA array data. The levels of hsa_circRNA_102209 in CRC specimens and cells, as well as its effects on CRC cells were investigated. The expression of hsa_circRNA_102209 in CRC and paired non-cancerous samples, human CRC, and normal colonic epithelial cells were examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cells with hsa_circRNA_102209 knockdown were established using lentiviral vectors. Cell proliferative ability was evaluated using CCK-8 assay; cell migrative/invasive activities were determined using wound healing/Transwell assay. Cell cycle arrest and apoptosis were assessed by flow cytometry; apoptosis, and EMT markers were examined using RT-qPCR and western blotting. Tumor development and levels of associated proteins were determined in hsa_circRNA_102209 knockdown mice. Our results revealed that expression of hsa_circRNA_102209 was remarkably increased in CRC tissues, where the levels of miR-761 were notably reduced (P < .05). Additionally, the levels of hsa_circRNA_102209 were associated with histology grade and occurrence of liver metastasis in CRC patients, and the expression of hsa_circRNA_102209 and miR-761 were negatively correlated (P < .05). Moreover, hsa_circRNA_102209 was upregulated in CRC cells compared with normal colonic epithelial cells. Knockdown of hsa_circRNA_102209 notably inhibited the proliferation, migration, invasion, and EMT of CRC cells (P < .05), whereas cell cycle arrest at G0/G1 phase and apoptosis were enhanced (P < .05). Furthermore, miR-761/Ras and Rab interactor 1 (RIN1) axis was the putative target of hsa_circRNA_102209 in CRC and involved in hsa_circRNA_102209-modulated growth and metastasis of CRC cells (P < .05). Knockdown of hsa_circRNA_102209 also remarkably suppressed tumor growth in vivo (P < .05). In summary, our data revealed that the expression of hsa_circRNA_102209 was elevated in CRC samples and cells. Furthermore, hsa_circRNA_102209 could promote the progression of CRC through miR-761/RIN1 axis. More importantly, hsa_circRNA_102209/miR-761/RIN1 signaling may be a novel therapeutic target for the treatment of CRC patients.
引用
收藏
页码:6710 / 6725
页数:16
相关论文
共 30 条
[1]  
[Anonymous], 2019, ANN R COLL SURG ENGL
[2]   Long Noncoding RNA H19 Promotes Proliferation and Invasion in Human Glioma Cells by Downregulating miR-152 [J].
Chen, Lei ;
Wang, Yuhai ;
He, Jianqing ;
Zhang, Chunlei ;
Chen, Junhui ;
Shi, Dongliang .
ONCOLOGY RESEARCH, 2018, 26 (09) :1419-1428
[3]   miR-15 and miR-16 induce apoptosis by targeting BCL2 [J].
Cimmino, A ;
Calin, GA ;
Fabbri, M ;
Iorio, MV ;
Ferracin, M ;
Shimizu, M ;
Wojcik, SE ;
Aqeilan, RI ;
Zupo, S ;
Dono, M ;
Rassenti, L ;
Alder, H ;
Volinia, S ;
Liu, CG ;
Kipps, TJ ;
Negrini, M ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (39) :13944-13949
[4]   The RNA Binding Protein Quaking Regulates Formation of circRNAs [J].
Conn, Simon J. ;
Pillman, Katherine A. ;
Toubia, John ;
Conn, Vanessa M. ;
Salmanidis, Marika ;
Phillips, Caroline A. ;
Roslan, Suraya ;
Schreiber, Andreas W. ;
Gregory, Philip A. ;
Goodall, Gregory J. .
CELL, 2015, 160 (06) :1125-1134
[5]   Molecular Genetics of Colorectal Cancer [J].
Fearon, Eric R. .
ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 6, 2011, 6 :479-+
[6]   Timeline - The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited [J].
Fidler, IJ .
NATURE REVIEWS CANCER, 2003, 3 (06) :453-458
[7]   Natural RNA circles function as efficient microRNA sponges [J].
Hansen, Thomas B. ;
Jensen, Trine I. ;
Clausen, Bettina H. ;
Bramsen, Jesper B. ;
Finsen, Bente ;
Damgaard, Christian K. ;
Kjems, Jorgen .
NATURE, 2013, 495 (7441) :384-388
[8]   cir-ITCH Plays an Inhibitory Role in Colorectal Cancer by Regulating the Wnt/β-Catenin Pathway [J].
Huang, Guanli ;
Zhu, Hua ;
Shi, Yixiong ;
Wu, Wenzhi ;
Cai, Huajie ;
Chen, Xiangjian .
PLOS ONE, 2015, 10 (06)
[9]   Global Cancer Statistics (vol 61, pg 69, 2011) [J].
Jemal, Ahmedin .
CA-A CANCER JOURNAL FOR CLINICIANS, 2011, 61 (02) :134-134
[10]   Circular RNA hsa_circ_0000523 regulates the proliferation and apoptosis of colorectal cancer cells as miRNA sponge [J].
Jin, Y. ;
Yu, L. L. ;
Zhang, B. ;
Liu, C. F. ;
Chen, Y. .
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH, 2018, 51 (12)