5p and 3p strands of miR-34 family members have differential effects in cell proliferation, migration, and invasion in cervical cancer cells
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The micro RNA (miR)-34 family is composed of 5p and 3p strands of miR-34a, miR-34b, and miR-34c. The 5p strand’s expression and function is studied in cervical cancer. The 3p strand’s function and regulation remain to be elucidated. To study the function of the passenger strands of miR-34 family members, we overexpressed 5p and 3p strands using a synthetic miRNA in cervical cell lines. Cell proliferation was evaluated using crystal violet. Migration and invasion were tested using transwell assays, Western blot, and zymography. Possible specific targets and cell signaling were investigated for each strand. We found that miR-34a-5p inhibited proliferation, migration, and cell invasion accompanied by matrix metalloproteinase 9 (MMP9) activity and microtubule-associated protein 2 (MAP2) protein reduction. We also found that miR-34b-5p and miR-34c-5p inhibit proliferation and migration, but not invasion. In contrast, miR-34c-5p inhibits MMP9 activity and MAP2 protein, while miR-34b-5p has no effect on these genes. Furthermore, miR-34a-3p and miR-34b-3p inhibit proliferation and migration, but not invasion, despite the later reducing MMP2 activity, while miR-34c-3p inhibit proliferation, migration, and cell invasion accompanied by MMP9 activity and MAP2 protein inhibition. The difference in cellular processes, MMP2 and MMP9 activity, and MAP2 protein inhibition by miR-34 family members suggests the participation of other regulated genes. This study provides insights into the roles of passenger strands (strand*) of the miR-34 family in cervical cancer. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
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Cell processes; Guide strand; MiR-34 family; Passenger strand cyclin D1; cyclin dependent kinase inhibitor 1; estrogen receptor alpha; gelatinase A; gelatinase B; growth factor receptor bound protein 2; immunoglobulin enhancer binding protein; lymphoid enhancer factor 1; microRNA; microRNA 34; microRNA 34a; microRNA 34b; microRNA 34c; microtubule associated protein 2; miR 34a 5p; miR 34b 5p; miR 34c 5p; mitogen activated protein kinase; mitogen activated protein kinase 3; Myc protein; phosphatidylinositol 3 kinase; phospholipase D1; platelet derived growth factor C; protein p21; serum response factor; stress activated protein kinase 1; T cell factor protein; transforming growth factor beta1; unclassified drug; unindexed drug; vasculotropin; microRNA; MIRN34 microRNA, human; apoptosis; Article; bioassay; cancer cell culture; cell invasion; cell migration; cell proliferation; cervical cancer cell line; computer prediction; controlled study; down regulation; gene control; gene expression; genetic transfection; human; human cell; metastasis; protein analysis; protein expression; radioimmunoprecipitation; regulatory mechanism; signal transduction; spectrophotometry; transwell assay; upregulation; uterine cervix cancer; Western blotting; zymography; cell motion; cell proliferation; computer simulation; female; gene expression regulation; genetics; metabolism; nucleotide sequence; pathology; tumor cell line; tumor invasion; uterine cervix tumor; Base Sequence; Cell Line, Tumor; Cell Movement; Cell Proliferation; Computer Simulation; Female; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Neoplasm Invasiveness; Uterine Cervical Neoplasms
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