RETRACTED ARTICLE: Functional studies of miR-130a on the inhibitory pathways of apoptosis in patients with chronic myeloid leukemia

Abstract

The p53 mutation in chronic myeloid leukemia (CML) led to decreased overall survival and therapy resistance which was also closely correlated with the downstream proto-oncogenes BCL-2, TCL-1 and MCL-1. We in this study aimed to investigate the function of miR130a in p53 tumor suppressor signaling pathway. We performed microRNA (miRNA) expression profile analysis in CML cancer stem cells of 38 cases and extracted total RNA from peripheral blood of 143 cases. Standard curves of U6 and miRNA were made from 10-fold serial dilutions of the cDNA, which were quantified using real-time quantitative PCR with SYBR Green by ABI 7300. The p53 mutations and BCR/ABL mutation status analysis in CML patients were detected by PCR and direct sequencing. Candidate targets of miR130a of putative relevance in CML pathogenesis were analyzed by bioinformatics approach. We then used dual-luciferase activity assay to verify the target genes of miR130a and used western blot analysis to elucidate the mechanism of miR130a on modulating drug resistance. The levels of miR-130a expression in CML were significantly lower in poor prognostic subgroups, defined by prognostic factors including mutated BCR/ABL status, p53 and ATM deletions and p53 mutations. Furthermore, underexpression of miR-130a was significantly associated with shorter overall survival and treatment-free survival in CML patients. We demonstrated that miR130a function as tumor suppressors by inhibiting multiple anti-apoptosis proteins, including BCL-2, MCL-1 and XIAP. This was a direct effect because miR130a negatively regulated expression of a BCL-2/MCL-1/XIAP 3'untranslated region-based reporter construct. Transfection of miR130a mimics into CML cells from 30 patients without p53 aberrations led to significant increases in apoptosis compared with transfection with the miRNA control. Besides, enforced expression of miR130a had no significant drug-sensitization effect in CML cells from p53-attenuated patients. MiR-130a may have an important role in the pathogenesis of CML and may be useful for assessing prognosis in patients with CML. Moreover, miR130a may provide a possible therapeutic avenue and a sensitive indicator of the activity of the p53 in CML.

MiR-130a-3p Inhibits PRL Expression and Is Associated With Heat Stress-Induced PRL Reduction

“…In previous studies, miR-130a-3p was usually reported to act as a tumor suppressor in various type of cancers (21,29,30) or a repressor in adipocyte tissue inhibiting the induction of preadipocytes into mature adipocytes (31). In this study, we firstly confirmed miR-130a-3p inhibited PRL expression, suggesting that miR-130a-3p may be involved in pituitary hormone regulation.…”

miR-130a Deregulates PTEN and Stimulates Tumor Growth

“…To date, the function of miR-130 family members in promoting cell proliferation and tumorigenesis has been controversial. While some reports have concluded that miR-130 family miRNAs can promote cell proliferation and are upregulated in several types of cancer (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39), other studies concluded that miR-130 family members inhibit cell proliferation and are downregulated in cancer (40)(41)(42)(43)(44)(45),highlighting the complexity of miR-130 function in tumorigenesis. Here we find that enforced miR-130a expression promotes cell proliferation in either MEFs or breast cancer cell lines while stimulating tumor growth in vivo through a PTEN-regulated process.…”

LncRNA FENDRR attenuates adriamycin resistance via suppressing MDR1 expression through sponging HuR and miR‐184 in chronic myelogenous leukaemia cells

“…Previous studies have found that many miRNAs are involved in drug resistance [21,22]. miR-130a can act as a tumour suppressor by targeting BCL2 and MCL-1 expression, lower expression of miR-130a is associated with poor prognosis in CML patients [23]. Otherwise, lncRNA SNHG5 promotes imatinib resistance through acting as a ceRNA against miR-205-5p with ABCC2 in CML [24].…”