Microchidia protein 2, MORC2, downregulates the cytoskeleton adapter protein, ArgBP2, via histone methylation in gastric cancer cells

Tong, Yuxin; Li, Yan; Gu, Hui; Wang, Chunyu; Liu, Funan; Shao, Yangguang; Li, Jiabin; Cao, Liu; Li, Feng

doi:10.1016/j.bbrc.2015.10.059

Cited by 26 publications

(23 citation statements)

References 29 publications

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Section: Discussionmentioning

confidence: 88%

“…In our previous study, we found that MORC2 could act as a transcriptional repressor and inhibit the transcription of a number of target genes, including CAIX, p21 Waf/Cip1 , and ArgBP2 in gastric cancer cells. [5][6][7] We also reported the potential role of the PAK1-MORC2 F I G U R E 6 Negative correlation of MORC2 and NDRG1 expression in colorectal cancer (CRC) samples. A, Representative images of immunohistochemical staining for CRC specimens incubated with MORC2 or NDRG1.…”

Section: Discussionmentioning

confidence: 99%

“…MORC2, also known as ZCWCC1, ZCW3, or KIAA0852, is a member of the MORC family of proteins. Our previous work showed that, in gastric cancer cells, MORC2 suppressed carbonic anhydrase IX ( CAIX ), p21 Waf1/Cip1 , and ArgBP2 (Arg‐binding protein 2) gene expression through histone deacetylase 4 (HDAC4), HDAC1, and EZH2, respectively. It has been reported that MORC2 facilitated chromatin remodeling following the DNA damage response and promoted lipogenesis .…”

Section: Introductionmentioning

confidence: 99%

“…EZH2, 7,8 respectively. It has been reported that MORC2 facilitated chromatin remodeling following the DNA damage response 9 and promoted lipogenesis.…”

mentioning

confidence: 99%

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MORC2 promotes development of an aggressive colorectal cancer phenotype through inhibition of NDRG1

Liu

Shao

et al. 2018

Cancer Science

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MORC2 (microrchidia family CW‐type zinc finger 2) is a newly identified chromatin remodeling protein that functions in diverse biological processes including gene transcription. NDRG1 is a metastasis suppressor and a prognostic biomarker for colorectal cancer (CRC). However, the relationship between MORC2 and NDRG1 transcriptional regulation and the roles of MORC2 in CRC remain elusive. Here, we showed that MORC2 downregulated NDRG1 mRNA, protein levels, and promoter activity in CRC cells. We also found that MORC2 bound to the −446 to −213 bp region of the NDRG1 promoter. Mechanistically, histone deacetylase sirtuin 1 (SIRT1) was involved in NDRG1 transcriptional regulation. MORC2 was able to interact with SIRT1 and inhibit NDRG1 promoter activity cumulatively with SIRT1. MORC2 overexpression led to a decrease of H3Ac and H4Ac of the NDRG1 promoter. Importantly, we showed that NDRG1 was essential in MORC2‐mediated promotion of CRC cell migration and invasion in vitro, as well as lung metastasis of CRC cells in vivo. Moreover, MORC2 expression correlated negatively with NDRG1 expression in CRC patients. High expression of MORC2 was significantly associated with lymph node metastasis (P = 0.019) and poor pTNM stage (P = 0.02) and the expression of MORC2 correlated with poor prognosis in colon cancer patients. Our findings thus contribute to the knowledge of the regulatory mechanism of MORC2 in downregulating NDRG1, and suggest MORC2 as a potential therapeutic target for CRC.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…EZH2, 7,8 respectively. It has been reported that MORC2 facilitated chromatin remodeling following the DNA damage response 9 and promoted lipogenesis.…”

mentioning

confidence: 99%

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MORC2 promotes development of an aggressive colorectal cancer phenotype through inhibition of NDRG1

Liu

Shao

et al. 2018

Cancer Science

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“…H3K27 monomethylation activates gene expression, whereas H3K27 dimethylation and trimethylation inhibit gene expression. For example, H3K27 trimethylation inhibits the expression of Arg kinase-binding protein 2 (ArgBP2) in gastric cancer [40]. …”

Section: The Histone Code Affects the Malignant Transformation Of Gasmentioning

confidence: 99%

Epigenetic roles in the malignant transformation of gastric mucosal cells

Tie

Zhang

Fan

2016

Cell. Mol. Life Sci.

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Gastric carcinogenesis occurs when gastric epithelial cells transition through the initial, immortal, premalignant, and malignant stages of transformation. Epigenetic regulations contribute to this multistep process. Due to the critical role of epigenetic modifications , these changes are highly likely to be of clinical use in the future as new biomarkers and therapeutic targets for the early detection and treatment of cancers. Here, we summarize the recent findings on how epigenetic modifications, including DNA methylation, histone modifications, and non-coding RNAs, regulate gastric carcinogenesis, and we discuss potential new strategies for the diagnosis and treatments of gastric cancer. The strategies may be helpful in the further understanding of epigenetic regulation in human diseases.

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The Emerging Role of MORC Family Proteins in Cancer Development and Bone Homeostasis

Hong

Qiu

Wang

et al. 2016

Journal Cellular Physiology

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Microrchidia (MORC or MORC family CW-type zinc finger protein), a highly conserved nuclear protein superfamily, is an interesting new player in signaling-dependent chromatin remodeling and epigenetic regulation. MORC family proteins consist of MORC1, MORC2, MORC3, and MORC4 which display common structural determinants such as CW-type zinc finger and coiled-coil domains. They also exhibit unique structural motifs and tissue-specific expression profiles. MORC1 was first discovered as a key regulator for male meiosis and spermatogenesis. Accumulating biochemical and functional analyses unveil MORC proteins as key regulators for cancer development. More recently, using an ENU mutagenesis mouse model, MORC3 was found to play a role in regulating bone and calcium homeostasis. Here we discuss recent research progress on the emerging role of MORC proteins in cancer development and bone metabolism. Unravelling the cellular and molecular mechanisms by which MORC proteins carry out their functions in a tissue specific manner are important subjects for future investigation. J. Cell. Physiol. 232: 928-934, 2017. © 2016 Wiley Periodicals, Inc.

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Microchidia protein 2, MORC2, downregulates the cytoskeleton adapter protein, ArgBP2, via histone methylation in gastric cancer cells

Cited by 26 publications

References 29 publications

MORC2 promotes development of an aggressive colorectal cancer phenotype through inhibition of NDRG1

MORC2 promotes development of an aggressive colorectal cancer phenotype through inhibition of NDRG1

Epigenetic roles in the malignant transformation of gastric mucosal cells

The Emerging Role of MORC Family Proteins in Cancer Development and Bone Homeostasis

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