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Long non-coding RNA MVIH promotes cell proliferation, migration, invasion through regulating multiple cancer-related pathways, and correlates with worse prognosis in pancreatic ductal adenocarcinomas.

ABSTRACT: We aimed to explore the effect of long non-coding RNA MVIH (lnc-MVIH) on cell proliferation, migration as well as invasion, and investigate the landscape of its molecular mechanism in pancreatic ductal adenocarcinomas (PDAC). Control overexpression (OE-NC group) and lnc-MVIH overexpression (OE-MVIH group) plasmids were transfected in BxPC-3 cells; control knock-down (KD-NC group) and lnc-MVIH knock-down (KD-MVIH group) plasmids were transfected in PANC-1 cells. Cellular functions were measured and mRNA sequencing was conducted. In 70 PDAC patients, lnc-MVIH expression in tumor and adjacent tissues was detected. Lnc-MVIH expression was higher in human PDAC cell lines than human normal pancreatic ductal epithelial cell line. Cell proliferation, migration and invasion were increased in OE-MVIH group compared to OE-NC group, but decreased in KD-MVIH group compared to KD-NC group. mRNA sequencing showed 145 differentially expressing genes (DEGs) upregulated in OE-MVIH group vs. OE-NC group and downregulated in KD-MVIH group vs. KD-NC group, and 51 DEGs downregulated in OE-MVIH group vs. OE-NC group and upregulated in KD-MVIH group vs. KD-NC group. These DEGs were enriched in several cancer-related pathways (including Hippo signaling pathway, cell cycle, Forkhead box O signaling pathway, apoptosis and advanced glycation end products-RAGE signaling pathway), and the effect of lnc-MVIH on regulating these DEGs was further validated by RT-qPCR. In PDAC patients, lnc-MVIH expression was increased in tumor tissue and correlated with advanced tumor size, lymph node metastasis, TNM stage and poor OS. In conclusion, lnc-MVIH might be a potential therapeutic target which regulated multiple cancer-related pathways in PDAC.

SUBMITTER: Hu S

PROVIDER: S-EPMC7270031 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Long non-coding RNA MVIH promotes cell proliferation, migration, invasion through regulating multiple cancer-related pathways, and correlates with worse prognosis in pancreatic ductal adenocarcinomas.

Hu Shaobo S Zheng Qichang Q Xiong Jiongxin J Wu Heshui H Wang Weici W Zhou Wei W

American journal of translational research 20200515 5

We aimed to explore the effect of long non-coding RNA MVIH (lnc-MVIH) on cell proliferation, migration as well as invasion, and investigate the landscape of its molecular mechanism in pancreatic ductal adenocarcinomas (PDAC). Control overexpression (OE-NC group) and lnc-MVIH overexpression (OE-MVIH group) plasmids were transfected in BxPC-3 cells; control knock-down (KD-NC group) and lnc-MVIH knock-down (KD-MVIH group) plasmids were transfected in PANC-1 cells. Cellular functions were measured a ...[more]

PMID: 32509206

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Project description:BackgroundPancreatic ductal adenocarcinoma (PDAC) is presently one of the cancers with the worst survival rates and least effective treatments. Moreover, total deaths due to PDAC are predicted to increase in the next 15 years. Therefore, novel insights into basic mechanism of PDAC development and therapies are needed. PDAC is characterized by a complex microenvironment, in which cancer and stromal cells release different molecules, such as ATP. ATP can be transported and/or exocytosed from active cancer cells and released from dying cells in the necrotic core of the cancer. We hypothesized that one of the ATP receptors, the P2X7 receptor (P2X7R) could be an important player in PDAC behaviour.MethodsWe determined the expression (real time PCR and Western blot) and localization (immunofluorescence) of P2X7R in human PDAC cell lines (AsPC-1, BxPC-3, Capan-1, MiaPaCa-2, Panc-1) and a "normal" human pancreatic duct epithelial cell line (HPDE). The function of P2X7R in proliferation (BrdU assay), migration (wound assay) and invasion (Boyden chamber with matrigel) was characterized. Furthermore, we studied P2X7R-dependent pore formation (YoPro-1 assay) and cell death (caspase and annexin V / propidium iodide assays).ResultsWe found higher expression of P2X7R protein in PDAC compared to HPDE cells. P2X7R had notable disparate effects on PDAC survival. Firstly, high concentrations of ATP or the specific P2X7R agonist, BzATP, had cytotoxic effects in all cell lines, and cell death was mediated by necrosis. Moreover, the P2X7R-pore antagonist, A438079, prevented ATP-induced pore formation and cell death. Second, in basal conditions and with low concentrations of ATP/BzATP, the P2X7R allosteric inhibitor AZ10606120 reduced proliferation in all PDAC cell lines. P2X7R also affected other key characteristics of cancer cell behavior. AZ10606120 reduced cell migration and invasion in PDAC cell lines compared to that of untreated/vehicle-treated control cells, and stimulation with sub-millimolar concentrations of ATP or BzATP substantially increased cell invasion.ConclusionsPDAC cell lines overexpress P2X7R and the receptor plays crucial roles in cell survival, migration and invasion. Therefore, we propose that drugs targeting P2X7R could be exploited in therapy of pancreatic cancer.

Dataset Information

Long non-coding RNA MVIH promotes cell proliferation, migration, invasion through regulating multiple cancer-related pathways, and correlates with worse prognosis in pancreatic ductal adenocarcinomas.

Publications

Long non-coding RNA MVIH promotes cell proliferation, migration, invasion through regulating multiple cancer-related pathways, and correlates with worse prognosis in pancreatic ductal adenocarcinomas.

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