MicroRNA-127 is aberrantly downregulated and acted as a functional tumor suppressor in human pancreatic cancer
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Pancreatic carcinoma is one of the most malignant human cancers. In this study, we intended to explore the molecular functional of microRNA-127 (miR-127) in regulating pancreatic cancer development both in vitro and in vivo. Quantitative real-time PCR (qRT-PCR) was performed to evaluate endogenous miR-127 expression in in vitro pancreatic cancer cell lines and in vivo clinical samples of pancreatic carcinoma. Lentiviral technology was applied to overexpress miR-127 in capan-1 and PANC-1 cells. Pancreatic cancer proliferation, cell-cycle progression, and invasion were assessed in vitro, and capan-1-derived tumorigenicity was evaluated in vivo. Dual-luciferase reporter assay and qRT-PCR were performed to assess the downstream target gene of miR-127 in pancreatic cancer, human Bcl-2-associated athanogene 5 (BAG5). BAG5 was subsequently upregulated in miR-127-overexpressed capan-1 and PANC-1 cells to evaluate its effect on pancreatic cancer progression. MiR-127 was preferentially downregulated in both pancreatic carcinoma cell lines and human pancreatic tumors. In lentivirus-infected capan-1 and PANC-1 cells, miR-127 overexpression significantly inhibited cancer progression, cell-cycle transition and invasion in vitro, as well as tumorigenicity in vivo. Human BAG5 was confirmed to be the downstream target of miR-127 in pancreatic cancer. Forced overexpression of BAG5 in capan-1 and PANC-1 cells reversed the tumor-suppressing effect of miR-127 on cancer development. MiR-127 is downregulated and acting as a tumor suppressor in pancreatic carcinoma. The functional regulation of miR-127 in pancreatic carcinoma is very likely through the inverse correlation of its downstream target gene of BAG5.
KeywordsPancreatic carcinoma miR-127 BAG5 Cancer proliferation Cancer migration Tumorigenicity
This work is supported by Grants from the National Natural Science Foundation of China (No.30872510, 81272534, 81260349, 81370569); and the Natural Science Foundation of Songjiang District (No.15SJGG23) and Key Program of Medical Specialty Construction in Shanghai City (ZK2015B20).
Compliance with ethical standards
Ethical approval for this study was granted by the Clinical Research and Ethic Committee at the Fifth People’s Hospital of Shanghai and Songjiang Hospital Affiliated to The First People’s Hospital of Shanghai Jiaotong University in Shanghai, China. Consent forms were signed by all participating patients. All protocols were performed in accordance with the Declaration of Helsinki and the guidelines for good clinical practice in China.
Conflicts of interest
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