miR-203, a Tumor Suppressor Frequently Down-regulated by Promoter Hypermethylation in Rhabdomyosarcoma

Diao, Yarui; Guo, Xing; Jiang, Lei; Wang, Gang; Zhang, Chao; Wan, Jun; Jin, Yan; Wu, Zhenguo

doi:10.1074/jbc.m113.494716

Cited by 77 publications

(65 citation statements)

References 89 publications

(110 reference statements)

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“…Importantly, the expression of miR-203 is drastically enhanced in the wound surrounding tissue [24][25][26][27]. Recent studies have shown that miR-203 can suppress Hesl expression [28]. Based on these results, we hypothesized that miR-203 may play a critical role in scar formation by suppressing Hes1 expression in the ESCs.…”

Section: Introductionmentioning

confidence: 99%

microRNA-203 Modulates Wound Healing and Scar Formation via Suppressing Hes1 Expression in Epidermal Stem Cells

Zhou

Shu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Little is known how miR-203 is involved in epidermal stem cells (ESCs) differentiation and scar formation. Methods: We first used luciferase assay to determine the interaction of miR-203 with the 3’-UTR in regulation of Hes1 expression. We then used flow cytometry to analyze the effects of miR-203 expression on the differentiation of ESCs to MFB by determination of CK15 ratio and α-SMA. To confirm the results of flow cytometry analysis, we used Western blot to examine the expression of α-SMA, Collagen I (Col I), and Collagen III (Col III), as well as the expression of Notch1, Jagged1, and Hes1 in ESCs after the treatment of pre-miR-203 or anti-miR-203. Finally, we examined the effects local anti-miR-203 treatment on would closure and scar formation using a mouse skin wound model. Results: Pre-miR-203 treatment increased ESCs differentiation to MFB cells, as indicated by decreased CK15 ratio and increased MFB biomarkers. This phenomenon was reversed by overexpression of Hes1 in ESCs. In addition, skin incision increased expression of miR-203 in wound tissue. Local treatment of anti-miR-203 could accelerate wound closure and reduce scar formation in vivo, which was associated with increased re-epithelialization, skin attachment regeneration, and collagen reassignment. Finally, we confirmed that anti-miR-203 treatment could inhibit ESCs differentiation in vivo via increasing Hesl expression. Conclusion: Taken together, our results suggested that overexpression of miR-203 in ESCs after skin wound may be a critical mechanism underlying the scar formation.

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Section: Introductionmentioning

confidence: 99%

microRNA-203 Modulates Wound Healing and Scar Formation via Suppressing Hes1 Expression in Epidermal Stem Cells

Zhou

Shu

et al. 2018

Cell Physiol Biochem

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“…Differential expression of miRNAs has been widely described in breast cancer tissue compared to normal tissue suggesting that miRNAs may function as oncogenes or tumorsuppressors (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

“…The hypermethylation of promoter CpG islands has been found to affect not only tumor-suppressor mRNAs, but also tumor-suppressor miRNAs. Several tumor-associated miRNAs have been reported to be silenced by the aberrant hypermethylation of their promoter regions in breast cancer, including miR-124, miR-34c, miR-148a, miR-155, miR-203 and miR-129 (3,(18)(19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of miR-129-2 by promoter hypermethylation regulates breast cancer cell proliferation and apoptosis

Tang

Liu

et al. 2016

Oncology Reports

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Abstract. Aberrant expression of the miR-129 family has been found in several types of cancer, yet its expression and potential biologic role in breast cancer remain largely unknown. In the present study, we found that miR-129-2 was consistently downregulated in the breast cancer specimens and cell lines. Overexpression of miR-129-2-3p markedly suppressed breast cancer cell proliferation and induced its apoptosis. In addition, a luciferase reporter assay revealed that miR-129-2-3p suppressed BCL2L2 expression. Furthermore, BCL2L2 was able to reverse miR-129-2-3p-mediated cell apoptosis, indicating that BCL2L2 plays a crucial role in mediating the tumor-suppressive role of miR-129-2-3p. Moreover, bisulfite DNA sequencing PCR (BSP) analysis identified that promoter hypermethylation was responsible for the downregulation of miR-129-2 in breast cancer. Collectively, our findings indicate that miR-129-2 is downregulated in breast cancer cells by promoter hypermethylation. Moreover, downregulation of miR-129-2 results in BCL2L2 overexpression and disease progression in breast cancer patients.

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“…Bioinformatics analysis identified IL8 as a putative target gene of miR-203 (18). MiR-203 is frequently downregulated and functions as a potential tumor suppressor in the various types of cancers, including NPC (19)(20)(21). Recent studies showed that the miR-203 expression level positively correlates with chemosensitivity in colon (22) and prostate (23) cancer cells.…”

Section: Introductionmentioning

confidence: 99%

MiRNA-203 Reduces Nasopharyngeal Carcinoma Radioresistance by Targeting IL8/AKT Signaling

et al. 2015

Molecular Cancer Therapeutics

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Radioresistance poses a major challenge in nasopharyngeal carcinoma (NPC) treatment, but little is known about how miRNA (miR) regulates this phenomenon. In this study, we investigated the function and mechanism of miR-203 in NPC radioresistance, one of downregulated miRs in the radioresistant NPC cells identified by our previous microarray analysis. We observed that miR-203 was frequently downregulated in the radioresistant NPC tissues compared with radiosensitive NPC tissues, and its decrement significantly correlated with NPC radioresistance and poor patient survival, and was an independent predictor for reduced patient survival. In vitro radioresponse assays showed that miR-203 mimic markedly decreased NPC cell radioresistance. In a mouse model, therapeutic administration of miR-203 agomir dramatically sensitized NPC xenografts to irradiation. Mechanistically, we confirmed that IL8 was a direct target of miR-203, and found that reduced miR-203 promoted NPC cell radioresistance by activating IL8/ AKT signaling. Moreover, the levels of IL8 and phospho-AKT were significantly increased in the radioresistant NPC tissues compared with radiosensitive NPC tissues, and negatively associated with miR-203 level. Our data demonstrate that miR-203 is a critical determinant of NPC radioresponse, and its decrement enhances NPC radioresistance through targeting IL8/AKT signaling, highlighting the therapeutic potential of the miR-203/IL8/AKT signaling axis in NPC radiosensitization. Mol Cancer Ther; 14(11); 2653-64. Ó2015 AACR.

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miR-203, a Tumor Suppressor Frequently Down-regulated by Promoter Hypermethylation in Rhabdomyosarcoma

Cited by 77 publications

References 89 publications

microRNA-203 Modulates Wound Healing and Scar Formation via Suppressing Hes1 Expression in Epidermal Stem Cells

microRNA-203 Modulates Wound Healing and Scar Formation via Suppressing Hes1 Expression in Epidermal Stem Cells

Downregulation of miR-129-2 by promoter hypermethylation regulates breast cancer cell proliferation and apoptosis

MiRNA-203 Reduces Nasopharyngeal Carcinoma Radioresistance by Targeting IL8/AKT Signaling

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