RETRACTED ARTICLE: Functional screen analysis reveals miR-3142 as central regulator in chemoresistance and proliferation through activation of the PTEN-AKT pathway in CML

Abstract

Chronic myeloid leukemia (CML) is caused by the constitutively active BCR-ABL tyrosine kinase. Although great progress has been made for improvement in clinical treatment during the past decades, it is common for patients to develop chemotherapy resistance. Therefore, further exploring novel therapeutic strategies are still crucial for improving disease outcome. MicroRNAs (miRNAs) represent a novel class of genes that function as negative regulators of gene expression. Recently, miRNAs have been implicated in several cancers. Previously, we identified 41 miRNAs that were dysregulated in resistant compared with adriamycin (ADR)-sensitive parental cells in CML. In the present study, we reported that miR-3142 are overexpressed in ADR-resistant K562/ADR cells and CML/multiple drug resistance patients, as compared with K562 cells and CML patients. Upregulation of miR-3142 in K562 cells accelerated colony formation ability and enhanced resisitance to ADR in vitro. Conversely, inhibition of miR-3142 expression in K562/ADR cells decreased colony-formation ability and enhanced sensitivity to ADR in vitro and in vivo. Significantly, our results showed miR-3142-induced ADR resistance through targeting phosphatase and tensin homologue deleted on chromosome 10 (PTEN), which led to downregulation of PTEN protein and activation of PI3 kinase (PI3K)/Akt pathway. Inhibition of Akt using Akt inhibitor or introduction of PTEN largely abrogated miR-3142-induced resistance. These findings indicated that miR-3142 induces cell proliferation and ADR resistance primarily through targeting the PTEN/PI3K/Akt pathway and implicate the potential application of miR-3142 in cancer therapy.

Combination of tanshinone IIA and doxorubicin possesses synergism and attenuation effects on doxorubicin in the treatment of breast cancer

“…PTEN is a major negative regulator of the AKT signaling, and its decreased expression or deletion activates AKT, thus phosphorylating the downstream apoptotic proteins and promoting cell survival, proliferation, and resistance (Shen et al, ; Zhao, Shan, Liu, Li, & Li, ). Therefore, we evaluated the expression of PTEN and p‐AKT in MCF‐7 and MCF‐7/dox cells.…”

A cytoplasmic long noncoding RNA LINC00470 as a new AKT activator to mediate glioblastoma cell autophagy

“…For example, nuclear AKT phosphorylates members of the Foxo subfamily of forkhead transcription factors, promoting nuclear exclusion and thereby inhibiting the transcription of death genes [ 13 , 14 ]. Evidence indicates that a number of positive regulators, including regulatory proteins (such as PI3K, PTEN, PDK1) [ 15 – 17 ], miRNAs (such as miRNA-7, miRNA-379, and miRNA-126) [ 18 – 21 ], and long noncoding RNAs (lncRNAs, such as LINK-A, lncRNA OIP5-AS1, and MALAT1), promote the overactivation of AKT signaling [ 22 – 24 ]. Until now, the underlying mechanism of AKT in the GBM was not fully understood despite many years of investigation.…”

Targeting P-Glycoprotein: Nelfinavir Reverses Adriamycin Resistance in K562/ADR Cells

“…Protein Kinase B, also known as Akt, regulates multiple biological processes, including cell survival, proliferation, growth, and glycogen metabolism [46]. The activation of the PI3K/Akt and MAPK/ERK pathway is related to the development of MDR in cancer cells [47][48][49]. Cancer cells are not sensitive to chemotherapeutic drugs, leading to a reduction in cell death caused by chemotherapeutic drugs, which leads to the emergence of drug resistance.…”