Arsenic disulfide promoted the demethylation of <i>PTPL1</i> in diffuse large B cell lymphoma cells.

Chen, Chen; Wang, Ling; Liu, Yan; Du, Shenghong; Teng, Qingliang

Arsenic disulfide promoted the demethylation of PTPL1 in diffuse large B cell lymphoma cells.

Chen, Chen; Wang, Ling; Liu, Yan; Du, Shenghong; Teng, Qingliang.

Afiliación

Chen C; Department of Hematology, The Affiliated Taian City Central Hospital of Qingdao University, Taian, Shandong, China.
Wang L; Department of Hematology, The Affiliated Taian City Central Hospital of Qingdao University, Taian, Shandong, China.
Liu Y; Department of Breast Surgery, The Affiliated Taian City Central Hospital of Qingdao University, Taian, Shandong, China.
Du S; Department of Hematology, The Affiliated Taian City Central Hospital of Qingdao University, Taian, Shandong, China.
Teng Q; Department of Hematology, The Affiliated Taian City Central Hospital of Qingdao University, Taian, Shandong, China.

PeerJ ; 12: e17363, 2024.

Article en En | MEDLINE | ID: mdl-38766487

ABSTRACT

ABSTRACT

Background:

Promoter hypermethylation of the tumor suppressor gene is one of the well-studied causes of cancer development. The drugs that reverse the process by driving demethylation could be a candidate for anticancer therapy. This study was designed to investigate the effects of arsenic disulfide on PTPL1 methylation in diffuse large B cell lymphoma (DLBCL).

Methods:

We knocked down the expression of PTPL1 in two DLBCL cell lines (i.e., DB and SU-DHL-4 cells) using siRNA. Then the DLBCL proliferation was determined in the presence of PTPL1 knockdown. The methylation of PTPL1 in DLBCL cells was analyzed by methylation specific PCR (MSPCR). The effect of arsenic disulfide on the PTPL1 methylation was determined in DLBCL cell lines in the presence of different concentrations of arsenic disulfide (5 µM, 10 µM and 20 µM), respectively. To investigate the potential mechanism on the arsenic disulfide-mediated methylation, the mRNA expression of DNMT1, DNMT3B and MBD2 was determined.

Results:

PTPL1 functioned as a tumor suppressor gene in DLBCL cells, which was featured by the fact that PTPL1 knockdown promoted the proliferation of DLBCL cells. PTPL1 was found hypermethylated in DLBCL cells. Arsenic disulfide promoted the PTPL1 demethylation in a dose-dependent manner, which was related to the inhibition of DNMTs and the increase of MBD2.

Conclusion:

Experimental evidence shows that PTPL1 functions as a tumor suppressor gene in DLBCL progression. PTPL1 hyper-methylation could be reversed by arsenic disulfide in a dose-dependent manner.

Asunto(s)

Arsenicales; Metilación de ADN; Linfoma de Células B Grandes Difuso; Humanos; Arsenicales/farmacología; Línea Celular Tumoral; Proliferación Celular/efectos de los fármacos; Disulfuros/farmacología; ADN (Citosina-5-)-Metiltransferasa 1/metabolismo; ADN (Citosina-5-)-Metiltransferasa 1/genética; ADN (Citosina-5-)-Metiltransferasas/genética; ADN (Citosina-5-)-Metiltransferasas/metabolismo; Metilación de ADN/efectos de los fármacos; ADN Metiltransferasa 3B; Proteínas de Unión al ADN/genética; Proteínas de Unión al ADN/metabolismo; Regulación Neoplásica de la Expresión Génica/efectos de los fármacos; Técnicas de Silenciamiento del Gen; Linfoma de Células B Grandes Difuso/tratamiento farmacológico; Linfoma de Células B Grandes Difuso/genética; Linfoma de Células B Grandes Difuso/patología; Regiones Promotoras Genéticas/efectos de los fármacos

Palabras clave

Arsenic disulfide; DNMTs; Demethylation; Diffuse large B cell lymphoma; MBD2

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arsenicales / Linfoma de Células B Grandes Difuso / Metilación de ADN Límite: Humans Idioma: En Revista: PeerJ Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos

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