MicroRNA-mediated regulation of pancreatic cancer cell proliferation

Abstract

Abstract. MicroRNAs (miRNAs) comprising 19-25 nucleotides are highly conserved small non-coding RNAs which regulate normal gene expression during development, cell proliferation and apoptosis by targeting mRNAs of protein-coding genes at the post-transcriptional level. Prevalent studies suggest that some human miRNAs, such as miRNA-16, are deregulated in human cancer and behave as tumor suppressors. The overall objective of our investigation was to assess whether miRNA-16 (miR-16) is involved in the regulation of critical genes, such as BCL2, that control the sensitivity of pancreatic cancer cells to apoptosis. This study showed that the ectopic overexpression of miR-16 may be therapeutically beneficial as is evidenced by impaired cell survival with concomitant attenuation of antiapoptotic protein Bcl-2. Moreover, the luciferase reporter assay suggested that miR-16 post-transcriptionally regulates Bcl-2 expression in pancreatic cancer cells through the target sites of the 3' untranslated region of this gene.

MicroRNA-375 and MicroRNA-221: Potential Noncoding RNAs Associated with Antiproliferative Activity of Benzyl Isothiocyanate in Pancreatic Cancer

“…It has been shown, thus, that miRNAs behave as both tumor suppressors and oncogenic entities. [1][2][3][4][5][6][7][8]37 In the present study, we report for the first time that the expression of putative oncogenic miRNAs such as miR-221 and tumor suppressor miR-375 can be altered upon BITC treatment of PDAC cells. Although miR-375 was initially shown to be expressed in pancreatic islets, 38 it is worth mentioning that in situ analyses revealed its presence also in pancreatic ductal epithelium.…”

“…Cells were plated at a density of 1.0 × 10 5 cells/mL in T75 flasks and incubated overnight at 37°C. 8 The following day, cells were transfected with 40 nM miR-221 miRIDIAN miRNA hairpin inhibitor (Dharmacon, Lafayette, CO) or 140 nM pre-miR-375 (Ambion) and their appropriate negative controls, using the DharmaFECT2 transfection reagent in accordance with the manufacturer's protocol (Dharmacon).…”

“…Immunoblotting was performed with p27 kip1 (BD Biosciences, Franklin Lakes, NJ), Caveolin-1 (R&D Systems, Minneapolis, MN), and IGFBP5 (Cayman Chemical, Ann Arbor, MI) primary antibodies as described previously. 8,13,14,16 Immunodetection with β-actin or α-tubulin antibody (Sigma, St. Louis, MO) served as a protein loading control.…”

“…The expression of microRNA (miRNA) signatures as well as individual miRNAs was observed to be connected with the diagnosis of a variety of human cancers including pancreatic carcinoma. [1][2][3][4][5][6][7][8][9][10][11][12] Pancreatic cells often become malignant during tumorigenesis when cells gain traits such as the ability to evade apoptosis, to replicate without bound, and to engage in persistent angiogenesis. [13][14][15][16] The emerging roles of miRNAs as oncogenes or tumor suppressors are prevalent in the literature.…”

“…[13][14][15][16] The emerging roles of miRNAs as oncogenes or tumor suppressors are prevalent in the literature. [2][3][4][8][9][10][11][12] Precisely, miRNAs may be considered as promising molecular targets for therapy of human pancreatic cancer.…”