title: MicroRNA miR-491-5p targeting both TP53 and Bcl-XL induces cell apoptosis in SW1990 pancreatic cancer cells through mitochondria mediated pathway.
abstract: MicroRNA (miRNA) actively participates in a broad range of cellular processes such as proliferation, differentiation, cell survival and apoptosis. Deregulated expression of miRNA may affect cell growth and eventually lead to cancer. In this study, we found that hsa-miR491-5p (miR491-5p) displays a significantly high level of expression in normal human pancreas tissue versus pancreatic cancer cells. Targeted site prediction indicated that both Bcl-XL and TP53 contain miR-491-5p recognizing sites in their 3' UTRs. Overexpression of miR-491-5p in the pancreatic cancer cell line SW1990 effectively inhibited both endogenous Bcl-XL and TP53 gene expressions. Mutagenesis at the seed match region of both targeted genes further confirmed the specificity of miR491-5p recognition. Cell proliferation rate was inversely related to the increased doses of miR-491-5p. Flow cytometric analysis showed that the proportions of total apoptotic and early apoptotic cells were significantly induced as the dose of miR491-5p increased. Moreover, a mechanistic study indicated that miR-R491-5p-mediated cell apoptosis was associated with the activation of intrinsic mitochondria mediated pathways. miR491-5p also markedly inhibited mitogenic signaling pathways such as STAT3 and PI-3K/Akt, but not Ras/MAPK. Thus, our results demonstrated that miR491-5p could effectively target both Bcl-xL and TP53 and induce cell apoptosis independent of TP53.
authors.affiliation: Department of Microbiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Guo
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Wei-Ye
authors.initials: WY
authors.lastname: Shi
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Sheng-Qi
authors.initials: SQ
authors.lastname: Hou
authors.forename: Li
authors.initials: L
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions; D000595:Amino Acid Sequence; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D010190:Pancreatic Neoplasms / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C494811:BCL2L1 protein, human; C551410:MIRN491 microRNA, human; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051020:bcl-X Protein; D019869:Phosphatidylinositol 3-Kinases