miR-34a sensitizes lung cancer cells to cisplatin via p53/miR-34a/MYCN axis

Song, Changshan; Lu, Ping; Sun, Guoqiang; Yang, Lin; Wang, Zhigang; Wang, Zheng

doi:10.1016/j.bbrc.2016.11.037

Cited by 41 publications

(32 citation statements)

References 29 publications

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“…For example, perturbation of miR-34a expression contributed to tumorigenesis by strongly attenuating p53-mediated apoptosis in human cancers [36]. In addition, p53 was found to monitor the expression of miR-34a after cisplatin and miR-34a targeted to MYCN to sensitize lung cancer cells to cisplatin [37]. It has been shown that miR-34a was identified as the most significantly highly expressed miRNA among TP53 alteration-associated miRNA profiles in acute myeloid leukemia with complex karyotype (CK-AML) [38].…”

Section: Discussionmentioning

confidence: 99%

MiR-34a Promotes Apoptosis and Inhibits Autophagy by Targeting HMGB1 in Acute Myeloid Leukemia Cells

Liu

Ren

Chen

2017

Cell Physiol Biochem

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Background: MiR-34a is identified as a tumor suppressor gene and involved in acute myeloid leukemia (AML) development. However, the regulatory mechanism of miR-34a in AML is unclear. Methods: The expression of miR-34a and HMGB1 in HL-60, THP-1 and HS-5 cells were detected by qRT-PCR and western blot. Lipofectamine 2000 was used to transfect with miR-34a mimics, miR-34a inhibitor, si-HMGB1, pcDNA 3.1-HMGB1, and corresponding controls. The apoptosis and autophagy of transfected AML cells were assessed by flow cytometry and western blot, respectively. Bioinformatics software and dual luciferase reporter assay were applied to predict and verify the target of miR-34a. The effects of miR-34a mimics or si-HMGB1 on chemotherapy-induced autophagy were further explored in HL-60 cells treated with all-trans retinoic acid (ATRA) along with lysosomal protease inhibitors E64d and pepstatin A. Results: MiR-34a was lower expressed and HMGB1 mRNA and proteins were both higher expressed in HL-60 and THP-1 cells compared with that in HS-5 cells. Higher expression levels of MiR-34 and lower expression levels of HMGB1 both significantly promoted apoptosis and inhibited autophagy in HL-60 and THP-1 cells. Dual luciferase reporter system confirmed that HMGB1 was a potential target of miR-34a. Moreover, overexpression of HMGB1 dramatically reversed the promotion of apoptosis and inhibition of autophagy mediated by higher expression level of miR-34a. Higher expression level of miR-34a and lower expression level of HMGB1 both inhibited chemotherapy-induced autophagy by stimulating the LC3 conversion. Conclusion: MiR-34a promoted cell apoptosis and inhibited autophagy by targeting HMGB1. Therefore, miR-34a may be a potential promising molecular target for AML therapy.

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Section: Discussionmentioning

confidence: 99%

MiR-34a Promotes Apoptosis and Inhibits Autophagy by Targeting HMGB1 in Acute Myeloid Leukemia Cells

Liu

Ren

Chen

2017

Cell Physiol Biochem

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“…Moreover, miR-34 could enhance the therapeutic efficacy of paclitaxel in resistant prostate cancer (106). Its overexpression enhanced cisplatin sensitivity, as confirmed in gastric cancer, by targeting MET (107) and in lung cancer, through the p53/MICN axis (108). Conversely, Pu et al found that miR-34a overexpression in osteosarcoma promoted resistance to several drugs (doxorubicin, etoposide, carboplatin, cisplatin), via repression of AGTR1 (109).…”

Section: A Network Analysis: the Most Central Ncrnas In Chemoresistancementioning

confidence: 90%

The Network of Non-coding RNAs in Cancer Drug Resistance

et al. 2018

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Non-coding RNAs (ncRNAs) have been implicated in most cellular functions. The disruption of their function through somatic mutations, genomic imprinting, transcriptional and post-transcriptional regulation, plays an ever-increasing role in cancer development. ncRNAs, including notorious microRNAs, have been thus proposed to function as tumor suppressors or oncogenes, often in a context-dependent fashion. In parallel, ncRNAs with altered expression in cancer have been reported to exert a key role in determining drug sensitivity or restoring drug responsiveness in resistant cells. Acquisition of resistance to anti-cancer drugs is a major hindrance to effective chemotherapy and is one of the most important causes of relapse and mortality in cancer patients. For these reasons, non-coding RNAs have become recent focuses as prognostic agents and modifiers of chemo-sensitivity. This review starts with a brief outline of the role of most studied non-coding RNAs in cancer and then highlights the modulation of cancer drug resistance via known ncRNAs based mechanisms. We identified from literature 388 ncRNA-drugs interactions and analyzed them using an unsupervised approach. Essentially, we performed a network analysis of the non-coding RNAs with direct relations with cancer drugs. Within such a machine-learning framework we detected the most representative ncRNAs-drug associations and groups. We finally discussed the higher integration of the drug-ncRNA clusters with the goal of disentangling effectors from downstream effects and further clarify the involvement of ncRNAs in the cellular mechanisms underlying resistance to cancer treatments.

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“…As mentioned previously, MYCN expression is frequently high in the developing lung epithelium and is important for epithelial mesenchymal interactions [6,182]. When the gene is mutated to a null allele or a conditional knock out in utero, there is a reduction in lung growth and reduced branching [6].…”

Section: Other Mycn-related Diseasesmentioning

confidence: 99%

“…When the gene is mutated to a null allele or a conditional knock out in utero, there is a reduction in lung growth and reduced branching [6]. Lung cancer is one of the most common cancers in the world [182,183]. Along with p53 and RB1 genomic alterations, amplification of the MYC family is observed in 20%–40% of small cell lung cancer (SCLC) cases [167,182,184,185].…”

Section: Other Mycn-related Diseasesmentioning

confidence: 99%

“…Lung cancer is one of the most common cancers in the world [182,183]. Along with p53 and RB1 genomic alterations, amplification of the MYC family is observed in 20%–40% of small cell lung cancer (SCLC) cases [167,182,184,185]. Lung cancer is unique in that all three MYC family members, c-MYC, MYCN and MYCL, are implicated in this disease and have been shown to activate or repress different subset of genes in SCLC cells [186].…”

Section: Other Mycn-related Diseasesmentioning

confidence: 99%

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The MYCN Protein in Health and Disease

Ruiz-Pérez

Henley

Arsenian-Henriksson

2017

Genes

130

110

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MYCN is a member of the MYC family of proto-oncogenes. It encodes a transcription factor, MYCN, involved in the control of fundamental processes during embryonal development. The MYCN protein is situated downstream of several signaling pathways promoting cell growth, proliferation and metabolism of progenitor cells in different developing organs and tissues. Conversely, deregulated MYCN signaling supports the development of several different tumors, mainly with a childhood onset, including neuroblastoma, medulloblastoma, rhabdomyosarcoma and Wilms’ tumor, but it is also associated with some cancers occurring during adulthood such as prostate and lung cancer. In neuroblastoma, MYCN-amplification is the most consistent genetic aberration associated with poor prognosis and treatment failure. Targeting MYCN has been proposed as a therapeutic strategy for the treatment of these tumors and great efforts have allowed the development of direct and indirect MYCN inhibitors with potential clinical use.

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miR-34a sensitizes lung cancer cells to cisplatin via p53/miR-34a/MYCN axis

Cited by 41 publications

References 29 publications

MiR-34a Promotes Apoptosis and Inhibits Autophagy by Targeting HMGB1 in Acute Myeloid Leukemia Cells

MiR-34a Promotes Apoptosis and Inhibits Autophagy by Targeting HMGB1 in Acute Myeloid Leukemia Cells

The Network of Non-coding RNAs in Cancer Drug Resistance

The MYCN Protein in Health and Disease

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