miR-143 inhibits the metastasis of pancreatic cancer and an associated signaling pathway

Abstract

Pancreatic cancer is characterized by early metastasis and high mortality. In this study, the role of miR-143 in invasion and metastasis was investigated in pancreatic cancer cells. miR-143 expression was established by an adenovirus-carried miR-143 expression cassette. mRNA and protein levels of gene expression were examined by RT-PCR and Western blot assay, respectively. Rho GTPases activity was measured by the pull down assay. The role of miR-143 in migration and invasion of Panc-1 cells was tested in vitro. The antimetastatic effect of miR-143 was tested in a liver metastasis model, while its antitumor growth effect was tested in a xenograft Panc-1 tumor model. Results demonstrated that ARHGEF1 (GEF1), ARHGEF2 (GEF2), and K-RAS genes are the targets of miR-143. miR-143 expression significantly decreased mRNA and protein levels of GEF1, GEF2, and K-RAS genes; lowered the constitutive activities of RhoA, Rac1, and Cdc42 GTPases; decreased the protein levels of MMP-2 and MMP-9; but significantly increased the protein level of E-cadherin. miR-143 expression also significantly inhibited the migration and invasion of Panc-1 cells in vitro, liver metastasis, and xenograft tumor growth in vivo. Our study suggested that miR-143 plays a central role in the invasion and metastasis of pancreatic cancer and miR-143 is a potential target for pancreatic cancer therapy.

MicroRNAs associated with small bowel neuroendocrine tumours and their metastases

“…In a metastatic mouse model of pancreatic cancer, miR-143 expression significantly reduced the formation of liver metastases (Hu et al 2012). Furthermore, xenograft pancreatic tumour growth was reduced by miR-143 through downregulating ARHGEF1, ARHGEF2 and KRAS, and reducing MMP-2 and MMP-9 protein levels, whilst increasing E-cadherin protein levels (Hu et al 2012). Importantly, putative interactions exist between miR-1/MMP-8 and miR-1/KRAS, and miR-143/KRAS and miR-143/ B,C,D).…”

“…This suggests that in prostate cancer, the functional loss of miR-143 or miR-145 may be cell-type-specific and results in bone metastasis, instead of LN metastasis (Peng et al 2011). Reduced miR-143 expression also plays a crucial role in the invasion and metastasis of pancreatic cancer (Hu et al 2012). In a metastatic mouse model of pancreatic cancer, miR-143 expression significantly reduced the formation of liver metastases (Hu et al 2012).…”

“…Reduced miR-143 expression also plays a crucial role in the invasion and metastasis of pancreatic cancer (Hu et al 2012). In a metastatic mouse model of pancreatic cancer, miR-143 expression significantly reduced the formation of liver metastases (Hu et al 2012). Furthermore, xenograft pancreatic tumour growth was reduced by miR-143 through downregulating ARHGEF1, ARHGEF2 and KRAS, and reducing MMP-2 and MMP-9 protein levels, whilst increasing E-cadherin protein levels (Hu et al 2012).…”

Role of microRNA-mediated MMP regulation in the treatment and diagnosis of malignant tumors

“…In Panc-1 cells, miR-143 expression significantly decreased MMP-2 and MMP-9 expression at the protein level and inhibited migration, invasion, liver metastasis, and xenograft tumor growth in vivo. 45 In addition to the previously outlined regulation of miR-125b, both gelatinases were also cancer, Merkel cell carcinoma, and HCC, and has generally been associated with poor prognoses. 10 However, to the best of our knowledge, the molecular mechanisms underlying the pathological activity of MMP- 21 have not yet been described.…”

MicroRNA-452 suppresses pancreatic cancer migration and invasion by directly targeting B-cell-specific Moloney murine leukemia virus insertion site 1

“…MicroRNAs (miRNAs/miRs) are considered to be useful biomarkers for the early diagnosis, therapy and prognosis of human cancers, including pancreatic cancer (8)(9)(10). They are an evolutionarily conserved group of non-protein-coding and short RNAs, 18-22 nucleotides in length, whose function is to regulate the expression of their target protein-coding genes either by translational suppression or gene degradation through binding to the 3' untranslated regions (3'UTRs) of target genes in a base-pairing manner (11,12).…”