Tumor suppressor role of miR-3622b-5p in ERBB2-positive cancer.
Over-expression or amplification of ERBB2 is observed in multifarious carcinomas. However, the molecular mechanism of ERBB2 downregulation in ERBB2-positive cancers remains obscure. This experiment investigated the suppressive role of miR-3622b-5p in ERBB2-positive breast and gastric cancers. The luciferase activity of ERBB2 3'-untranslated region-based reporters constructed in HEK-293T, SK-BR-3 and MCF-10A cells suggested that ERBB2 was the target gene of miR-3622b-5p. Over-expressed miR-3622b-5p reduced the protein level of ERBB2, weakened the activation of mTORC1/S6, and induced the apoptosis of ERBB2-positive cancer cells. MiR-3622b-5p was significantly down-regulated in breast and gastric cancer tissues. This down-regulation in ERBB2-positive breast and gastric cancer tissues was more obvious than that in ERBB2-negative breast and gastric cancer tissues. MiR-3622b-5p turned ERBB2-positive cancer cells more vulnerable to the apoptosis induced by cisplatin and 5-fluorouracil. Taken together, miR-3622b-5p is involved in the proliferation and apoptosis of human ERBB2-positive cancer cells via targeting ERBB2/mTORC1 signaling pathway.
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.
Mingjie
M
Lu
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.
Tongshan
T
Wang
Department of Anesthesiology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.
Mingfeng
M
He
Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.
Wenfang
W
Cheng
Safety Assessment and Research Center for Drug, Pesticide and Veterinary Drug of Jiangsu Province, Nanjing Medical University, Nanjing 211166, PR China.
Ting
T
Yan
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.
Zebo
Z
Huang
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.
Lan
L
Zhang
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.
Huo
H
Zhang
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.
Wei
W
Zhu
Department of Physiology, Nanjing Medical University, Nanjing 211166, PR China.|State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, PR China.
Yichao
Y
Zhu
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.
Ping
P
Liu
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation; D016147:Genes, Tumor Suppressor; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014162:Transfection
D035683:MicroRNAs; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
ERBB2; apoptosis; cancer; miR-3622b-5p; proliferation