MiR-17-5p regulates cell proliferation and migration by targeting transforming growth factor-β receptor 2 in gastric cancer.
TGFBR2 serves as an initial regulator of the TGF-β signaling pathway, and loss or reduction of its expression leads to uncontrolled cell growth and invasion. TGFBR2 plays a crucial role in the carcinogenesis and malignant process of gastric cancer, but the mechanism remains unclear. In this study, we found that TGFBR2 protein levels were consistently upregulated in gastric cancer tissues, whereas TGFBR2 mRNA levels varied among these tissues, indicating that a post-transcriptional mechanism is involved in the regulation of TGFBR2. MiRNAs are known to regulate gene expression at the post-transcriptional level. Therefore, we performed bioinformatics analyses to search for miRNAs potentially targeting TGFBR2. MiR-17-5p was found to bind to the 3'UTR of TGFBR2 mRNA, and further validation of this specific binding was performed through a reporter assay. An inverse correlation between miR-17-5p and TGFBR2 protein was observed in gastric cancer tissues. Cell studies revealed that miR-17-5p negatively regulated TGFBR2 expression by directly binding to the 3'UTR of TGFBR2 mRNA, thereby promoting cell growth and migration. We also validated the role of TGFBR2 using siRNA and an overexpression plasmid. The results of our study suggest a novel regulatory network in gastric cancer mediated by miR-17-5p and TGFBR2 and may indicate that TGFBR2 could serve as a new therapeutic target in gastric cancer.
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Yanjun
Y
Qu
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Haiyang
H
Zhang
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Jingjing
J
Duan
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Rui
R
Liu
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Ting
T
Deng
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Ming
M
Bai
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Dingzhi
D
Huang
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Hongli
H
Li
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Tao
T
Ning
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Le
L
Zhang
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Xia
X
Wang
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Shaohua
S
Ge
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Likun
L
Zhou
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Benfu
B
Zhong
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Guoguang
G
Ying
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Yi
Y
Ba
D020413:3' Untranslated Regions; D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019295:Computational Biology; D030541:Databases, Genetic; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014162:Transfection
D020413:3' Untranslated Regions; C524941:MIRN17 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II
TGFBR2; cell proliferation; gastric cancer; miR-17-5p; migration