The Effect of MicroRNA-124 Overexpression on Anti-Tumor Drug Sensitivity

Chen, Shiau Mei; Chou, Wen Cheng; Hu, Ling; Hsiung, Chia Ni; Chu, Hou Wei; Huang, Yuan; Hsu, Huan Ming; Yu, Jyh Cherng; Shen, Chen

doi:10.1371/journal.pone.0128472

Cited by 39 publications

(33 citation statements)

References 49 publications

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“…Moreover, miR-124 was found to be downregulated in gefitinib-resistant non-small cell lung cancer (NSCLC) cells, and overexpression of miR-124 sensitized gefitinib-resistant cells to gefitinib [34]. Also, miR-124 was found to be a potential therapeutic agent to improve the efficacy of chemotherapy with DNA-damaging agents in breast cancer [35]. Our study demonstrated that miR-124 expression was downregulated in DOX-resistant CRC tissues Cellular Physiology and Biochemistry Cellular Physiology and Biochemistry and cells.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of Long Non-Coding RNA XIST Inhibited Doxorubicin Resistance in Colorectal Cancer by Upregulation of miR-124 and Downregulation of SGK1

Zhu

Zhang

Yang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Doxorubicin (DOX) is a widely used chemotherapeutic agent for colorectal cancer (CRC). However, the acquirement of DOX resistance limits its clinical application for cancer therapy. Mounting evidence has suggested that aberrantly expressed lncRNAs contribute to drug resistance of various tumors. Our study aimed to explore the role and molecular mechanisms of lncRNA X-inactive specific transcript (XIST) in chemoresistance of CRC to DOX. Methods: The expressions of XIST, miR-124, serum and glucocorticoid-inducible kinase 1 (SGK1) mRNA in DOX-resistant CRC tissues and cells were detected by qRT-PCR or western blot analysis. DOX sensitivity was assessed by detecting IC50 value of DOX, the protein levels of P-glycoprotein (P-gp) and glutathione S-transferase-π (GST-π) and apoptosis. The interactions between XIST, miR-124 and SGK1 were confirmed by luciferase reporter assay, qRT-PCR and western blot. Xenograft tumor assay was used to verify the role of XIST in DOX resistance in CRC in vivo. Results: XIST expression was upregulated and miR-124 expression was downregulated in DOX-resistant CRC tissues and cells. Knockdown of XIST inhibited DOX resistance of CRC cells, as evidenced by the reduced IC50 value of DOX, decreased P-gp and GST-π levels and enhanced apoptosis in XIST-silenced DOX-resistant CRC cells. Additionally, XIST positively regulated SGK1 expression by interacting with miR-124 in DOX-resistant CRC cells. miR-124 suppression strikingly reversed XIST-knockdown-mediated repression on DOX resistance in DOX-resistant CRC cells. Moreover, SGK1-depletion-elicited decrease of DOX resistance was greatly restored by XIST overexpression or miR-124 inhibition in DOX-resistant CRC cells. Furthermore, XIST knockdown enhanced the anti-tumor effect of DOX in CRC in vivo. Conclusion: XIST exerted regulatory function in resistance of DOX possibly through miR-124/SGK1 axis, shedding new light on developing promising therapeutic strategy to overcome chemoresistance in CRC patients.

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Section: Discussionmentioning

confidence: 99%

Knockdown of Long Non-Coding RNA XIST Inhibited Doxorubicin Resistance in Colorectal Cancer by Upregulation of miR-124 and Downregulation of SGK1

Zhu

Zhang

Yang

et al. 2018

Cell Physiol Biochem

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“…Emerging evidence has indicated that miRNAs are involved in the anti-cancer effects of many reagents [22]. MiR-21 is an oncogenic miRNA and is over-expressed in malignant glioma [23,24].…”

Section: Introductionmentioning

confidence: 99%

AKT Axis, miR-21, and RECK Play Pivotal Roles in Dihydroartemisinin Killing Malignant Glioma Cells

Shao

Zhang

et al. 2017

IJMS

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Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, is known to play important roles in inhibiting proliferation rate, inducing apoptosis, as well as hindering the metastasis and invasion of glioma cells, but the underlying mechanisms are still unclear so far. In this study, methyl thiazolyl tetrazolium (MTT), colony-forming, wound healing, invasion, and apoptosis assays were performed to investigate the effect of DHA on malignant glioma cells. Results showed that DHA induced apoptosis of malignant glioma cells through Protein Kinase B (AKT) axis, induced death of malignant glioma cells by downregulating miR-21, and inhibited the invasion of malignant glioma cells corresponding with up-regulation of the reversion-inducing-cysteine-rich protein with kazal motifs (RECK). These results revealed that AKT axis, miR-21, and RECK play pivotal roles in DHA killing malignant glioma cells, suggesting that DHA is a potential agent for treating glioma.

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“…www.microrna.org ) showed that multiple p53 or HIF-dependent miRs are predicted to bind to the ATMIN transcript, including miR-373 (a HIF-1α target) and miR-34 (a p53 target) 12 37 38 . In addition, a recent study, which screened for the miR-124 targets involved in the DNA damage response, found ATMIN to be regulated by miR-124 39 . Importantly, miR-124 is a known direct target of p53 suggesting that it is likely to be involved in down-regulation of ATMIN under hypoxia 40 .…”

Section: Discussionmentioning

confidence: 99%

Mechanisms and consequences of ATMIN repression in hypoxic conditions: roles for p53 and HIF-1

Leszczynska

Göttgens

Biasoli

et al. 2016

Sci Rep

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Hypoxia-induced replication stress is one of the most physiologically relevant signals known to activate ATM in tumors. Recently, the ATM interactor (ATMIN) was identified as critical for replication stress-induced activation of ATM in response to aphidicolin and hydroxyurea. This suggests an essential role for ATMIN in ATM regulation during hypoxia, which induces replication stress. However, ATMIN also has a role in base excision repair, a process that has been demonstrated to be repressed and less efficient in hypoxic conditions. Here, we demonstrate that ATMIN is dispensable for ATM activation in hypoxia and in contrast to ATM, does not affect cell survival and radiosensitivity in hypoxia. Instead, we show that in hypoxic conditions ATMIN expression is repressed. Repression of ATMIN in hypoxia is mediated by both p53 and HIF-1α in an oxygen dependent manner. The biological consequence of ATMIN repression in hypoxia is decreased expression of the target gene, DYNLL1. An expression signature associated with p53 activity was negatively correlated with DYNLL1 expression in patient samples further supporting the p53 dependent repression of DYNLL1. Together, these data demonstrate multiple mechanisms of ATMIN repression in hypoxia with consequences including impaired BER and down regulation of the ATMIN transcriptional target, DYNLL1.

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The Effect of MicroRNA-124 Overexpression on Anti-Tumor Drug Sensitivity

Cited by 39 publications

References 49 publications

Knockdown of Long Non-Coding RNA XIST Inhibited Doxorubicin Resistance in Colorectal Cancer by Upregulation of miR-124 and Downregulation of SGK1

Knockdown of Long Non-Coding RNA XIST Inhibited Doxorubicin Resistance in Colorectal Cancer by Upregulation of miR-124 and Downregulation of SGK1

AKT Axis, miR-21, and RECK Play Pivotal Roles in Dihydroartemisinin Killing Malignant Glioma Cells

Mechanisms and consequences of ATMIN repression in hypoxic conditions: roles for p53 and HIF-1

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