HPV-16 E6 upregulation of DNMT1 through repression of tumor suppressor p53

Chi Lam Au Yeung; Wing Pui Tsang; Tsun Yee Tsang; Ngai Na Co; Pak Lun Yau; Tim Tak Kwok

doi:10.3892/or-00001023

HPV-16 E6 upregulation of DNMT1 through repression of tumor suppressor p53

Chi Lam Au Yeung, Wing Pui Tsang, Tsun Yee Tsang, Ngai Na Co, Pak Lun Yau, Tim Tak Kwok

Gynecological Oncology & Reproductive Medicine

Research output: Contribution to journal › Article › peer-review

108 Scopus citations

Abstract

The HPV-16 early proteins E6 and E7 are considered to function as oncoproteins in cervical cancer. DNA methyltransferase 1 (DNMT1) is one of the enzymes involved in epigenetic silencing of tumor suppressor genes. In the present study, the functional role and regulation of DNMT1 in HPV-16 E6 associated cervical cancer development were examined. Knockdown of E6 in HPV-16 positive human cervical carcinoma SiHa and CaSki cells led to the increase in p53, repression of DNMT1 protein and promoter activity. Moreover, p53 knockdown increased the DNMT1 protein as well as promoter activity, indicating that p53 may mediate E6 upregulation of DNMT1. In addition, E6 knockdown induced growth retardation in SiHa cells, and the effect was partially reverted by DNMT1 overexpression. The results suggest that HPV-16 E6 may act through p53/DNMT1 to regulate the development of cervical cancer.

Original language	English (US)
Pages (from-to)	1599-1604
Number of pages	6
Journal	Oncology reports
Volume	24
Issue number	6
DOIs	https://doi.org/10.3892/or-00001023
State	Published - Dec 2010

Keywords

Cervical cancer
DNMT1
HPV-16 E6
p53

ASJC Scopus subject areas

Oncology
Cancer Research

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10.3892/or-00001023

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title = "HPV-16 E6 upregulation of DNMT1 through repression of tumor suppressor p53",

abstract = "The HPV-16 early proteins E6 and E7 are considered to function as oncoproteins in cervical cancer. DNA methyltransferase 1 (DNMT1) is one of the enzymes involved in epigenetic silencing of tumor suppressor genes. In the present study, the functional role and regulation of DNMT1 in HPV-16 E6 associated cervical cancer development were examined. Knockdown of E6 in HPV-16 positive human cervical carcinoma SiHa and CaSki cells led to the increase in p53, repression of DNMT1 protein and promoter activity. Moreover, p53 knockdown increased the DNMT1 protein as well as promoter activity, indicating that p53 may mediate E6 upregulation of DNMT1. In addition, E6 knockdown induced growth retardation in SiHa cells, and the effect was partially reverted by DNMT1 overexpression. The results suggest that HPV-16 E6 may act through p53/DNMT1 to regulate the development of cervical cancer.",

keywords = "Cervical cancer, DNMT1, HPV-16 E6, p53",

author = "Yeung, {Chi Lam Au} and Tsang, {Wing Pui} and Tsang, {Tsun Yee} and Co, {Ngai Na} and Yau, {Pak Lun} and Kwok, {Tim Tak}",

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T1 - HPV-16 E6 upregulation of DNMT1 through repression of tumor suppressor p53

AU - Yeung, Chi Lam Au

AU - Tsang, Wing Pui

AU - Tsang, Tsun Yee

AU - Co, Ngai Na

AU - Yau, Pak Lun

AU - Kwok, Tim Tak

PY - 2010/12

Y1 - 2010/12

N2 - The HPV-16 early proteins E6 and E7 are considered to function as oncoproteins in cervical cancer. DNA methyltransferase 1 (DNMT1) is one of the enzymes involved in epigenetic silencing of tumor suppressor genes. In the present study, the functional role and regulation of DNMT1 in HPV-16 E6 associated cervical cancer development were examined. Knockdown of E6 in HPV-16 positive human cervical carcinoma SiHa and CaSki cells led to the increase in p53, repression of DNMT1 protein and promoter activity. Moreover, p53 knockdown increased the DNMT1 protein as well as promoter activity, indicating that p53 may mediate E6 upregulation of DNMT1. In addition, E6 knockdown induced growth retardation in SiHa cells, and the effect was partially reverted by DNMT1 overexpression. The results suggest that HPV-16 E6 may act through p53/DNMT1 to regulate the development of cervical cancer.

AB - The HPV-16 early proteins E6 and E7 are considered to function as oncoproteins in cervical cancer. DNA methyltransferase 1 (DNMT1) is one of the enzymes involved in epigenetic silencing of tumor suppressor genes. In the present study, the functional role and regulation of DNMT1 in HPV-16 E6 associated cervical cancer development were examined. Knockdown of E6 in HPV-16 positive human cervical carcinoma SiHa and CaSki cells led to the increase in p53, repression of DNMT1 protein and promoter activity. Moreover, p53 knockdown increased the DNMT1 protein as well as promoter activity, indicating that p53 may mediate E6 upregulation of DNMT1. In addition, E6 knockdown induced growth retardation in SiHa cells, and the effect was partially reverted by DNMT1 overexpression. The results suggest that HPV-16 E6 may act through p53/DNMT1 to regulate the development of cervical cancer.

KW - Cervical cancer

KW - DNMT1

KW - HPV-16 E6

KW - p53

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JO - Oncology reports

JF - Oncology reports

IS - 6

ER -

HPV-16 E6 upregulation of DNMT1 through repression of tumor suppressor p53

Abstract

Keywords

ASJC Scopus subject areas

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