MicroRNA-155 promotes apoptosis in SKOV3, A2780, and primary cultured ovarian cancer cells

Abstract

MicroRNAs (miRNAs) are a large group of small non-coding RNAs that can negatively regulate gene expression at the post-transcriptional level. The deregulation of miRNAs has been associated with tumorigenesis, drug resistance, and prognosis in cancers. Deregulated miR-155 has been reported in numerous cancers; however, its function remains unclear. 4',6-Diamidino-2-phenylindole (DAPI) staining and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) techniques were used to determine the effects of a miR-155 mimic or inhibitor on the apoptotic ratio of ovarian cancer cells induced by cisplatin. Bioinformatic predictions, the dual-luciferase reporter assay, and western blot analysis were used to detect how miR-155 regulates X-linked inhibitor of apoptosis protein (XIAP). We demonstrated that a miR-155 mimic could decrease the IC50 value of cisplatin in SKOV3 ovarian cancer cells. Subsequently, gain- and loss-of-function analyses with a miR-155 mimic and inhibitor showed that miR-155 sensitizes ovarian cancer cells to cisplatin. Furthermore, the results from the luciferase assays and western blot analysis identified XIAP as the direct target of miR-155. In addition, introducing XIAP cDNA without a three prime untranslated region (3'-UTR) rescued the miR-155 promotion of apoptosis. These results indicate that miR-155 mediates cisplatin-induced apoptosis by targeting XIAP in ovarian cancer cells and that miR-155 could be a potential therapeutic target to increase the efficiency of ovarian cancer interventions.

miR‐155expression in antitumor immunity: The higher the better?

“…Accordingly, transfecting SKOV3, A2780, and primary cultured ovarian cancer cells with a miR‐155 mimic increased their sensibility to cisplatin. This effect was due to miR‐155 targeting the 3′‐untranslated region of transcripts encoding X‐linked inhibitor of apoptosis protein (XIAP) . In mouse, increasing miR‐155 levels in tumor‐associated dendritic cells reprogrammed them from immunosuppressive cells to cells with improved antigen‐presenting capacity that induced a stronger antigen‐specific T cell proliferation at tumor location, leading to the presence of a higher proportion of antigen‐experienced CD4 + and CD8 + T cells and abrogating the progression of established ovarian cancer .…”

“…This effect was due to miR-155 targeting the 3 0 -untranslated region of transcripts encoding X-linked inhibitor of apoptosis protein (XIAP). 84 In mouse, increasing miR-155 levels in tumor-associated dendritic cells reprogrammed them from immunosuppressive cells to cells with improved antigen-presenting capacity that induced a stronger antigen-specific T cell proliferation at tumor location, leading to the presence of a higher proportion of antigen-experienced CD4 + and CD8 + T cells and abrogating the progression of established ovarian cancer. 85 However, a 2-2.5-fold increase in miR-155 expression was found in pancreatic cancer tissues compared with matched normal pancreas controls, and a 1.88-fold increase in miR-155 expression was found in pancreatic cancer compared with chronic pancreatitis.…”

The Value of Plasma-Based MicroRNAs as Diagnostic Biomarkers for Ovarian Cancer

“…These miRNAs were produced by tumor-induced systemic responses. [23][24][25] Zhou et al 13 described in their research that "circulating miRNAs were believed to be passively leaked or actively transported from cells during tumorigenesis and packaged into small membranous vesicles or protected by the formation of a protein-miRNA complex, and the miRNAs with low expression levels in tumor tissue might be broken down in tissues and then released into the bloodstream." However, the exact mechanism needs to be further studied.…”

miR-155 mediates arsenic trioxide resistance by activating Nrf2 and suppressing apoptosis in lung cancer cells

“…Moreover, overexpression of miR-155 in lung cancer cells inhibits the expression level of forkhead box O3 (FOXO3a) protein that mediates cell apoptosis, decreasing the sensitivity of lung cancer cells to gefitinib 32 . In addition, miR-155 is actively involved in the chemotherapeutic drug resistance by downregulating a series of pro-apoptotic proteins that include tumor protein p53-inducible nuclear protein 1 (TP53INP1), X-linked inhibitor of apoptosis protein (XIAP), and suppressor of cytokine signaling 6 (SOCS6) among others 33 , 34 . Thus, it is likely that miR-155 may mediate ATO resistance in A549R cells by inhibiting cell apoptosis through downregulation of Apaf-1, FOXO3a, TP53INP1, XIAP, and SOCS6.…”