MEF2C promotes gefitinib resistance in hepatic cancer cells through regulating MIG6 transcription

Zhang, Hui; Liu, Wei; Wang, Zhi; Meng, Lin; Wang, Yunhua; Yan, Huawu; Lin, Li

doi:10.1177/0300891618765555

Cited by 11 publications

(7 citation statements)

References 50 publications

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“…MIG-6 (or ERRFI1) is a negative regulator of all members of the ErbB receptor family, and involvement of the EGFR signaling pathway has been investigated (Endo et al, 2017). Research indicates that ERRFI1 plays an important role in the response of cancer cells to chemotherapeutic agents (Li et al, 2014;Zhang et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of KHSRP sensitizes colorectal cancer to 5‐fluoruracil through miR‐501‐5p‐mediated ERRFI1 mRNA degradation

Pan

Cai

Sun

et al. 2019

Journal Cellular Physiology

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K-homology (KH)-type splicing regulatory protein (KHSRP) is an RNA binding protein that participates in RNA variable splicing and stability, and facilitates the biogenesis of miRNAs that target mRNA. However, to date, the role of KHSRP in colorectal cancer (CRC) progression has not been reported. In this study, the function of KHSRP in CRC proliferation and 5-fluoruracil (5-FU) resistance was investigated. The upregulation of KHSRP expression was confirmed in CRC patient tissues and two CRC cell lines. Manipulating KHSRP expression altered cell proliferation and 5-FU resistance in CRC cells. ERRFI1, a downstream effector of KHSRP in CRC cells, reduced CRC cell proliferation. Sensitivity to 5-FU mediated by KHSRP knockdown was reversed by ERRFI1 knockdown. We found that KHSRP decreased ERRFI1 mRNA expression indirectly. By screening KHSRP-regulated miRNAs, we further found that miR-501-5p directly combines with KHSRP in CRC cells. Mechanistically, the results of a luciferase assay suggested that miR-501-5p directly binds to the ERRFI1 3ʹ-untranslated region. Taken together, our data indicated that modification of ERRFI1 by KHSRP occurs through miR-501-5p, an essential mechanism driving CRC proliferation and 5-FU resistance. Insight into this mechanism may provide novel targets for overcoming drug resistance in CRC. K E Y W O R D S 5-FU resistance, colorectal cancer, ERRFI1, KHSRP, miR-501-5p SUPPORTING INFORMATION Additional supporting information may be found online in the Supporting Information section. How to cite this article: Pan R, Cai W, Sun J, Yu C, Li P, Zheng M. Inhibition of KHSRP sensitizes colorectal cancer to 5fluoruracil through miR-501-5p-mediated ERRFI1 mRNA degradation.

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Section: Discussionmentioning

confidence: 99%

Inhibition of KHSRP sensitizes colorectal cancer to 5‐fluoruracil through miR‐501‐5p‐mediated ERRFI1 mRNA degradation

Pan

Cai

Sun

et al. 2019

Journal Cellular Physiology

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“…Agatheeswaran et al found that MEF2C is overexpressed in myeloid leukemia 28 . Zhang et al observed an increased MEF2C in liver cancer, whereas its knockdown inhibits cell growth and protects cancer cells against chemoresistance 29 . Ni et al demonstrated that silencing of MEF2C not only represses endometrial carcinoma metastasis and proliferation of cells in vitro but also hampers tumor xenograft growth in vivo 30 .…”

Section: Discussionmentioning

confidence: 99%

“… 28 Zhang et al observed an increased MEF2C in liver cancer, whereas its knockdown inhibits cell growth and protects cancer cells against chemoresistance. 29 Ni et al demonstrated that silencing of MEF2C not only represses endometrial carcinoma metastasis and proliferation of cells in vitro but also hampers tumor xenograft growth in vivo. 30 Herein, we also observed that MEF2C was overexpressed in OS cells and tumors, suggesting that MEF2C may also be an underlying onco‐protein in OS progression.…”

Section: Discussionmentioning

confidence: 99%

Silencing of lncRNA KLF3‐AS1 represses cell growth in osteosarcoma via miR‐338‐3p/MEF2C axis

Chen

Liu

2022

Clinical Laboratory Analysis

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Osteosarcoma (OS) is a severe bone malignancy mainly occurring among adolescents under twenty-five years old. 1 It is generally characterized by bone pain and dysfunction. 2 Although various options for OS treatment, such as aggressive surgery and chemoradiotherapy, have improved the 5-year survival rate to approximately 60%, some OS patients still suffered from high rate of recurrence. 3 Therefore, comprehending the pathogenesis of OS is imperative to formulate efficacious therapeutic procedures.Long non-coding RNA (lncRNA) are 200 nt in length and can regulate post-transcription. 4 LncRNAs have been reported to have

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“…MEF2C-mediated VEGF-induced vasculogenic mimicry, angiogenesis, and invasion, as well as inhibition of β-catenin-induced tumor growth ( Bai et al, 2015 ). Besides, MEF2C was upregulated in gefitinib-resistant cancer tissues and associated with gefitinib resistance in hepatic cancer cells ( Zhang et al, 2018 ). He et al (2021) found that EOMES was down expressed in tissue samples and related to the advanced stage and poor prognosis of hepatocellular carcinoma.…”

Section: Discussionmentioning

confidence: 99%

A Novel Overall Survival Prediction Signature Based on Cancer Stem Cell-Related Genes in Osteosarcoma

Xiao

Liu²,

Chen

et al. 2021

Front. Cell Dev. Biol.

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Background: Osteosarcoma is the most general bone malignancy that mostly affects children and adolescents. Numerous stem cell-related genes have been founded in distinct forms of cancer. This study aimed at identifying a stem cell-related gene model for the expected assessment of the prognosis of osteosarcoma patients.Methods: We obtained the genes expression data and relevant clinical materials from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. We identified differentially expressed genes (DEGs) from the GEO dataset, whereas prognostic stem cell-related genes were obtained from the TARGET database. Subsequently, univariate, LASSO and multivariate Cox regression analyses were applied to establish the stem cell-related signature. Finally, the prognostic value of the signature was validated in the GEO dataset.Results: Twenty-five genes were prognostic ferroptosis-related DEGs. Consequently, we identified eight stem cell-related genes as a signature of prognosis of osteosarcoma patients. Then, the Kaplan–Meier (K-M) curve, the AUC value of ROC, and Cox regression analysis verified that the eight stem cell-related gene model were a new and substantial prognostic marker independent of other clinical traits. Moreover, the nomogram on the foundation of risk score and other clinical traits was established for predicting the survival rate of osteosarcoma patients. Biological function analyses displayed that tumor related pathways were affluent.Conclusion: The expression level of stem cell-related genes offers novel prognostic markers as well as underlying therapeutic targets for the therapy and prevention of osteosarcoma.

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MEF2C promotes gefitinib resistance in hepatic cancer cells through regulating MIG6 transcription

Abstract: Our study provides novel insight into the regulation mechanism of MIG6 and suggests potential implications for the therapeutic strategies of gefitinib resistance through inhibiting MEF2C in hepatic cancer cells.

Cited by 11 publications

References 50 publications

Inhibition of KHSRP sensitizes colorectal cancer to 5‐fluoruracil through miR‐501‐5p‐mediated ERRFI1 mRNA degradation

Inhibition of KHSRP sensitizes colorectal cancer to 5‐fluoruracil through miR‐501‐5p‐mediated ERRFI1 mRNA degradation

Silencing of lncRNA KLF3‐AS1 represses cell growth in osteosarcoma via miR‐338‐3p/MEF2C axis

A Novel Overall Survival Prediction Signature Based on Cancer Stem Cell-Related Genes in Osteosarcoma

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