MicroRNA-127 is aberrantly downregulated and acted as a functional tumor suppressor in human pancreatic cancer

Abstract

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.

Tumor Suppressor Function of miR-127-3p and miR-376a-3p in Osteosarcoma Cells

“…Downregulation of miR-127 has been shown to be a common feature in several types of cancer, including ovarian cancer [27], gastric cancer [28], squamous cell carcinoma [26], pancreatic cancer [31], giant cell tumor of bone [35], and osteosarcoma [36]. Likewise, downregulation of miR-376a has…”

“…Downregulation of miR-127 has been shown to be a common feature in several types of cancer, including ovarian cancer [27], gastric cancer [28], squamous cell carcinoma [26], pancreatic cancer [31], giant cell tumor of bone [35], and osteosarcoma [36]. Likewise, downregulation of miR-376a has been reported in multiple cancer types, including breast cancer [32], lymphoma [30], non-small-cell lung cancer [29], giant cell tumor of bone [35], and osteosarcoma [37].…”

“…MiR-127 and miR-376a have frequently been reported to be silenced in several types of cancer, suggesting pivotal roles for the development and progression of cancer [25][26][27][28][29][30][31][32]. We hypothesized that these miRNAs might also be silenced in highly malignant osteosarcoma, thus representing valuable targets for the improvement of current osteosarcoma therapy.…”

Transcriptome Profiling of Panc-1 Spheroid Cells with Pancreatic Cancer Stem Cells Properties Cultured by a Novel 3D Semi-Solid System

“…Two miRNAs (miR-374a-3p, miR-340-5p) have yet to be associated with pancreatic cancer but involved in other types of cancer [20,21]. Furthermore, of the top 10 miRNAs down-regulated in spheroids, five miRNAs (miR-486-3p, miR-134-5p, miR-320a, miR-127-3p, and miR-377-3p) have been reported previously to be related to pancreatic cancer, and three of them were found playing an important role in drug resistance (miR320a) [22], cell proliferation (miR-377-3p) [23], or as a tumor suppressor (miR-127-3p) [24],while the other two miRNAs had no further study yet. Four miRNAs, miR-370-3p, miR-185-5p, miR-193a-5p and miR-378a-3p were all associated with chemoresistance and involved in other types of cancer [25][26][27][28].…”

miR‑493 inhibits proliferation and invasion in pancreatic cancer cells and inversely regulated hERG1 expression

“…Although surgery is the primary way of treatment, pharmacological treatments are also an important adjuvant to surgery. During the past decades, studies have tried to understand the undelying molecular and signaling mechanisms that regulate the development of PC so that better therapy strategies may be developed ( 4 – 6 ).…”