Methyltransferase DNMT3B promotes colorectal cancer cell proliferation by inhibiting PLCG2

Aberrant DNA methylation patterns in the promoter region of PLCG2 are associated with dysregulated signaling pathways and cellular functions. Its role in colorectal cancer cells is still unknown. In this study, qRT-PCR is used to measure D...

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Main Authors: Ji Yong, Wang Yang, Zou Jiacheng, Liu Guanghao, Xia Mingyu, Ren Jun, Wang Daorong
Format: Article
Language:English
Published: China Science Publishing & Media Ltd. 2024-08-01
Series:Acta Biochimica et Biophysica Sinica
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Online Access:https://www.sciengine.com/doi/10.3724/abbs.2024117
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author Ji Yong
Wang Yang
Zou Jiacheng
Liu Guanghao
Xia Mingyu
Ren Jun
Wang Daorong
author_facet Ji Yong
Wang Yang
Zou Jiacheng
Liu Guanghao
Xia Mingyu
Ren Jun
Wang Daorong
author_sort Ji Yong
collection DOAJ
description Aberrant DNA methylation patterns in the promoter region of PLCG2 are associated with dysregulated signaling pathways and cellular functions. Its role in colorectal cancer cells is still unknown. In this study, qRT-PCR is used to measure DNMT3B expression in colorectal cancer. Western blot analysis and immunohistochemistry are used to analyze DNMT3B and PLCG2 protein levels in colorectal tissues and cell lines. Cell Counting Kit-8 (CCK-8) and colony formation assays are used to assess the proliferation of colorectal cancer cells. Methylation-specific PCR (MSP) and bisulfite-sequencing PCR (BSP) are used to measure DNA methylation level. Our results show that DNMT3B is overexpressed in colorectal cells in the TCGA datasets according to Kaplan-Meier plots. DNMT3B is significantly overexpressed in tumor tissues compared to that in adjacent nontumor tissues. Western blot analysis results demonstrate high expression of DNMT3B in tumor tissues. Compared to normal colonic epithelial cells, colorectal cancer cell lines exhibit elevated level of PLCG2 methylation. Overexpression of PLCG2 effectively prevents the growth of colorectal cancer xenograft tumors in vivo. PLCG2 is identified as a key downstream regulatory protein of DNMT3B in colorectal cancer. DNMT3B inhibits PLCG2 transcription through methylation of the PLCG2 promoter region. DNMT3B controls colorectal cancer cell proliferation through PLCG2, which is useful for developing therapeutic approaches that target PLCG2 expression for the treatment of colorectal cancer.
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publisher China Science Publishing & Media Ltd.
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spelling doaj-art-7d2065db42eb40bdbfa229a1d6c2e0532025-01-17T05:58:26ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452024-08-01561848185910.3724/abbs.202411720d259ccMethyltransferase DNMT3B promotes colorectal cancer cell proliferation by inhibiting PLCG2Ji Yong0Wang Yang1Zou Jiacheng2Liu Guanghao3Xia Mingyu4Ren Jun5Wang Daorong6["The Yangzhou School of Clinical Medicine of Dalian Medical University, Yangzhou 225001, China","Jingjiang People’s Hospital, Jingjiang 214500, China","General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou 225001, China","Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou 225001, China"]["Clinical Medical College, Yangzhou University, Yangzhou 225001, China","General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou 225001, China","Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou 225001, China"]["The Yangzhou School of Clinical Medicine of Dalian Medical University, Yangzhou 225001, China","General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou 225001, China","Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou 225001, China"]["Clinical Medical College, Yangzhou University, Yangzhou 225001, China","General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou 225001, China","Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou 225001, China"]["The Yangzhou Clinical Medical College of Xuzhou Medical University, Yangzhou 225001, China","General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou 225001, China","Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou 225001, China"]["Clinical Medical College, Yangzhou University, Yangzhou 225001, China","General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou 225001, China","Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou 225001, China"]["The Yangzhou School of Clinical Medicine of Dalian Medical University, Yangzhou 225001, China","Clinical Medical College, Yangzhou University, Yangzhou 225001, China","General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou 225001, China","Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou 225001, China"]Aberrant DNA methylation patterns in the promoter region of PLCG2 are associated with dysregulated signaling pathways and cellular functions. Its role in colorectal cancer cells is still unknown. In this study, qRT-PCR is used to measure DNMT3B expression in colorectal cancer. Western blot analysis and immunohistochemistry are used to analyze DNMT3B and PLCG2 protein levels in colorectal tissues and cell lines. Cell Counting Kit-8 (CCK-8) and colony formation assays are used to assess the proliferation of colorectal cancer cells. Methylation-specific PCR (MSP) and bisulfite-sequencing PCR (BSP) are used to measure DNA methylation level. Our results show that DNMT3B is overexpressed in colorectal cells in the TCGA datasets according to Kaplan-Meier plots. DNMT3B is significantly overexpressed in tumor tissues compared to that in adjacent nontumor tissues. Western blot analysis results demonstrate high expression of DNMT3B in tumor tissues. Compared to normal colonic epithelial cells, colorectal cancer cell lines exhibit elevated level of PLCG2 methylation. Overexpression of PLCG2 effectively prevents the growth of colorectal cancer xenograft tumors in vivo. PLCG2 is identified as a key downstream regulatory protein of DNMT3B in colorectal cancer. DNMT3B inhibits PLCG2 transcription through methylation of the PLCG2 promoter region. DNMT3B controls colorectal cancer cell proliferation through PLCG2, which is useful for developing therapeutic approaches that target PLCG2 expression for the treatment of colorectal cancer.https://www.sciengine.com/doi/10.3724/abbs.2024117epigeneticsDNA methylationDNMT3BPLCG2colorectal cancer
spellingShingle Ji Yong
Wang Yang
Zou Jiacheng
Liu Guanghao
Xia Mingyu
Ren Jun
Wang Daorong
Methyltransferase DNMT3B promotes colorectal cancer cell proliferation by inhibiting PLCG2
Acta Biochimica et Biophysica Sinica
epigenetics
DNA methylation
DNMT3B
PLCG2
colorectal cancer
title Methyltransferase DNMT3B promotes colorectal cancer cell proliferation by inhibiting PLCG2
title_full Methyltransferase DNMT3B promotes colorectal cancer cell proliferation by inhibiting PLCG2
title_fullStr Methyltransferase DNMT3B promotes colorectal cancer cell proliferation by inhibiting PLCG2
title_full_unstemmed Methyltransferase DNMT3B promotes colorectal cancer cell proliferation by inhibiting PLCG2
title_short Methyltransferase DNMT3B promotes colorectal cancer cell proliferation by inhibiting PLCG2
title_sort methyltransferase dnmt3b promotes colorectal cancer cell proliferation by inhibiting plcg2
topic epigenetics
DNA methylation
DNMT3B
PLCG2
colorectal cancer
url https://www.sciengine.com/doi/10.3724/abbs.2024117
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