Overexpression of the Transcription Factor MEF2D in Hepatocellular Carcinoma Sustains Malignant Character by Suppressing G2–M Transition Genes

Ma, Leina; Liu, Jia; Liu, Limei; Duan, Guangjie; Wang, Qingliang; Xu, Yan; Xia, Feng; Shan, Juanjuan; Shen, Junjie; Yang, Zhi; Bie, Ping; Cui, You‐Hong; Bian, Xiu‐Wu; Prieto, Jesús; Avila, Matı́as A.; Qian, Cheng

doi:10.1158/0008-5472.can-13-2171

Cited by 76 publications

(75 citation statements)

References 44 publications

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“…The transcription factor MEF2D promotes the survival of various types of cells and functions as an oncogene in liver cancer (17,21,22). Zhao et al reported that oleanolic acid (OA) suppressed the proliferation of lung carcinoma cells (23).…”

Section: Discussionmentioning

confidence: 99%

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Absent expression of miR‑30a promotes the growth of lung cancer cells by targeting MEF2D

2018

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Abstract. The microRNA (miR)-30 family has been reported to be aberrantly expressed in several types of cancer. However, its contributions to lung cancer remain to be fully elucidated. Myocyte enhancer factor 2D (MEF2D), an oncogene in liver cancer, has been shown to be aberrantly expressed in lung cancer. In the present study, it was found that MEF2D and miR-30a were inversely correlated in lung cancer samples. Using an online database, it was predicted that miR-30a targeted the 3' untranslated region (UTR) of MEF2D mRNA. The activity of luciferase with MEF2D 3'UTR was suppressed by transfecting cells with miR-30a mimics. The results of western blot analysis showed that the miR-30a mimics also suppressed the MEF2D protein. The miR-30a mimics were able to reduce the growth and colonies of lung cancer cells by suppressing MEF2D. The results of FACS and western blot assays showed that the apoptotic rate was reduced by transfection with the miR-30a mimics. Collectively, the aberrant expression of miR-30a in lung cancer promoted the expression of MEF2D protein. miR-30a inhibited the growth and colony formation of the lung cancer cells by promoting apoptosis.

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Section: Discussionmentioning

confidence: 99%

“…Western blot analyses were performed as described by Ma et al (17). Total protein was extracted and quantified using Beyotime protein systems (pre-chilled lysis buffer, cat.…”

Section: Analysis Of Apoptosismentioning

confidence: 99%

Absent expression of miR‑30a promotes the growth of lung cancer cells by targeting MEF2D

2018

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“…Altered MEF2 activity serves a role in human diseases and it has recently been implicated in the initiation and progression of various types of cancer in humans (31). Recently, it was reported that MEF2D, one member of MEF2 family, is involved in the progression of several cancer types, including lung carcinoma (27), rhabdomyosarcoma (32), hepatocellular carcinoma (31) and osteosarcoma (25).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of miR‑30a is associated with proliferation and invasion via targeting MEF2D in cervical cancer

Zhao

Shu

et al. 2017

Oncol Lett

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Abstract. Accumulating studies have revealed that microRNAs serve crucial roles in cancer development and progression. MicroRNA-30a (miR-30a) has been implicated in various cancer types. However, the role of miR-30a in cervical cancer remains unclear. In the current study, a reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay revealed that miR-30a was significantly downregulated in cervical cancer tissues compared with adjacent normal tissues, and in the cervical cancer cell lines HeLa, SiHa and Ca-Ski compared with GH329 normal cervical epithelial cells. A functional assay using miR-30a mimic demonstrated that miR-30a could inhibit the growth and invasion of cervical cancer cells. Additionally, bioinformatics-based prediction and luciferase reporter assays indicated that MEF2D is a direct target of miR-30a. Transfection with miR-30a reduced the mRNA expression and protein levels of MEF2D, as determined using RT-qPCR and western blot analyses. Furthermore, MEF2D expression was negatively correlated with that of miR-30a in cervical cancers. Overall, the present study demonstrated that miR-30a functions as a tumor suppressor by targeting MEF2D in cervical cancer, which may provide the basis for a prognostic biomarker or therapeutic strategy for cervical cancer.

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“…It has been recently reported that MEF2D protein negatively regulates the expression of Gadd45b and p21 genes and binds to MEF2 sites in their promoter sequences in hepatocellular carcinoma (HCC) cell lines. 57 Thus it may be argued that MEF2C induces directly the expression of these G2/M transition inhibitors. In contrast, our bioinformatic analysis did not reveal any MEF2 site in the promoter region of 14-3-3g, suggesting a possible indirect control of MEF2C on this gene.…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation-dependent degradation of MEF2C contributes to regulate G2/M transition

et al. 2015

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The Myocyte Enhancer Factor 2C (MEF2C) transcription factor plays a critical role in skeletal muscle differentiation, promoting muscle-specific gene transcription. Here we report that in proliferating cells MEF2C is degraded in mitosis by the Anaphase Promoting Complex/Cyclosome (APC/C) and that this downregulation is necessary for an efficient progression of the cell cycle. We show that this mechanism of degradation requires the presence on MEF2C of a D-box (R-X-X-L) and 2 phospho-motifs, pSer98 and pSer110. Both the D-box and pSer110 motifs are encoded by the ubiquitous alternate a1 exon. These two domains mediate the interaction between MEF2C and CDC20, a co-activator of APC/C. We further report that in myoblasts, MEF2C regulates the expression of G2/M checkpoint genes (14-3-3g, Gadd45b and p21) and the sub-cellular localization of CYCLIN B1. The importance of controlling MEF2C levels during the cell cycle is reinforced by the observation that modulation of its expression affects the proliferation rate of colon cancer cells. Our findings show that beside the well-established role as pro-myogenic transcription factor, MEF2C can also function as a regulator of cell proliferation.

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Overexpression of the Transcription Factor MEF2D in Hepatocellular Carcinoma Sustains Malignant Character by Suppressing G2–M Transition Genes

Cited by 76 publications

References 44 publications

Absent expression of miR‑30a promotes the growth of lung cancer cells by targeting MEF2D

Absent expression of miR‑30a promotes the growth of lung cancer cells by targeting MEF2D

Downregulation of miR‑30a is associated with proliferation and invasion via targeting MEF2D in cervical cancer

Phosphorylation-dependent degradation of MEF2C contributes to regulate G2/M transition

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