YY1 is a novel potential therapeutic target for the treatment of HPV infection YInduced cervical cancer by arsenic trioxide

Guifen He, Qian Wang, Yuqi Zhou, Xiaohua Wu, Lan Wang, Nadire Duru, Xiangtao Kong, Pingzhao Zhang, Bo Wan, Long Sui, Qisang Guo, Jian-Jian Li, Long Yu

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Objective: YY1 is a zinc finger transcription factor involved in the regulation of cell growth, development, and differentiation. Although YY1 can regulate human papillomavirusYtype (HPV) viral oncogenes E6 and E7, it remains unknown if YY1 plays a key role in carcinoma progression of HPV-infected cells. Here we sought to determine whether YY1 is upregulated in the cervical cancer tissues and YY1 inhibition contributes to apoptosis of cervical cancer cells, which is at least partly p 53 dependent. Therefore, YY1 can be a potential therapeutic target for cervical cancer treatment by arsenic trioxide (As 2O 3). Materials and Methods: The expression level of YY1 was examined and analyzed by Western blot in pathologically confirmed primary cervical cancer samples, in the adjacent normal samples, as well as in normal cervix samples. The effects of YY1 inhibition by specific small interfering RNA in HeLa cells were determined by Western blot analysis of p 53 level, cell growth curve, colony formation assay, and apoptosis. The contribution of YY1 to As 2O 3-induced p 53 activation and apoptosis was also examined by Western blot and cell cycle analysis. Results: Here we report that the expression level of YY1 is significantly elevated in the primary cancer tissues. In HPV-positive HeLa cells, small interfering RNAYmediated YY1 inhibition induced apoptosis and increased the expression of p 53. Treatment of HeLa cells with As 2O 3, a known antiYcervical cancer agent, reduced both protein and mRNA levels of YY1 in HeLa cells. YY1 knockdown significantly further enhanced As 2O 3- induced apoptosis. Conclusions: These results demonstrated that the expression of YY1 is upregulated in cervical carcinomas and that YY1 plays a critical role in the progression of HPV-positive cervical cancer. In addition, YY1 inhibition induces p 53 activation and apoptosis in HPVinfected HeLa cells. Thus, YY1 is an As 2O 3 target and could serve as a potential drug sensitizer for antiYcervical cancer therapy.

Original languageEnglish (US)
Pages (from-to)1097-1104
Number of pages8
JournalInternational Journal of Gynecological Cancer
Volume21
Issue number6
DOIs
StatePublished - Aug 2011

Fingerprint

Uterine Cervical Neoplasms
HeLa Cells
Apoptosis
Infection
Western Blotting
Therapeutics
Carcinoma
Neoplasms
Zinc Fingers
Growth and Development
Oncogenes
Cervix Uteri
Small Interfering RNA
arsenic trioxide
Cell Cycle
Transcription Factors
Messenger RNA
Growth
Pharmaceutical Preparations
Proteins

Keywords

  • Arsenic trioxide
  • Cervical cancer
  • Therapeutic target
  • YY1

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

YY1 is a novel potential therapeutic target for the treatment of HPV infection YInduced cervical cancer by arsenic trioxide. / He, Guifen; Wang, Qian; Zhou, Yuqi; Wu, Xiaohua; Wang, Lan; Duru, Nadire; Kong, Xiangtao; Zhang, Pingzhao; Wan, Bo; Sui, Long; Guo, Qisang; Li, Jian-Jian; Yu, Long.

In: International Journal of Gynecological Cancer, Vol. 21, No. 6, 08.2011, p. 1097-1104.

Research output: Contribution to journalArticle

He, Guifen ; Wang, Qian ; Zhou, Yuqi ; Wu, Xiaohua ; Wang, Lan ; Duru, Nadire ; Kong, Xiangtao ; Zhang, Pingzhao ; Wan, Bo ; Sui, Long ; Guo, Qisang ; Li, Jian-Jian ; Yu, Long. / YY1 is a novel potential therapeutic target for the treatment of HPV infection YInduced cervical cancer by arsenic trioxide. In: International Journal of Gynecological Cancer. 2011 ; Vol. 21, No. 6. pp. 1097-1104.
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abstract = "Objective: YY1 is a zinc finger transcription factor involved in the regulation of cell growth, development, and differentiation. Although YY1 can regulate human papillomavirusYtype (HPV) viral oncogenes E6 and E7, it remains unknown if YY1 plays a key role in carcinoma progression of HPV-infected cells. Here we sought to determine whether YY1 is upregulated in the cervical cancer tissues and YY1 inhibition contributes to apoptosis of cervical cancer cells, which is at least partly p 53 dependent. Therefore, YY1 can be a potential therapeutic target for cervical cancer treatment by arsenic trioxide (As 2O 3). Materials and Methods: The expression level of YY1 was examined and analyzed by Western blot in pathologically confirmed primary cervical cancer samples, in the adjacent normal samples, as well as in normal cervix samples. The effects of YY1 inhibition by specific small interfering RNA in HeLa cells were determined by Western blot analysis of p 53 level, cell growth curve, colony formation assay, and apoptosis. The contribution of YY1 to As 2O 3-induced p 53 activation and apoptosis was also examined by Western blot and cell cycle analysis. Results: Here we report that the expression level of YY1 is significantly elevated in the primary cancer tissues. In HPV-positive HeLa cells, small interfering RNAYmediated YY1 inhibition induced apoptosis and increased the expression of p 53. Treatment of HeLa cells with As 2O 3, a known antiYcervical cancer agent, reduced both protein and mRNA levels of YY1 in HeLa cells. YY1 knockdown significantly further enhanced As 2O 3- induced apoptosis. Conclusions: These results demonstrated that the expression of YY1 is upregulated in cervical carcinomas and that YY1 plays a critical role in the progression of HPV-positive cervical cancer. In addition, YY1 inhibition induces p 53 activation and apoptosis in HPVinfected HeLa cells. Thus, YY1 is an As 2O 3 target and could serve as a potential drug sensitizer for antiYcervical cancer therapy.",
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author = "Guifen He and Qian Wang and Yuqi Zhou and Xiaohua Wu and Lan Wang and Nadire Duru and Xiangtao Kong and Pingzhao Zhang and Bo Wan and Long Sui and Qisang Guo and Jian-Jian Li and Long Yu",
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T1 - YY1 is a novel potential therapeutic target for the treatment of HPV infection YInduced cervical cancer by arsenic trioxide

AU - He, Guifen

AU - Wang, Qian

AU - Zhou, Yuqi

AU - Wu, Xiaohua

AU - Wang, Lan

AU - Duru, Nadire

AU - Kong, Xiangtao

AU - Zhang, Pingzhao

AU - Wan, Bo

AU - Sui, Long

AU - Guo, Qisang

AU - Li, Jian-Jian

AU - Yu, Long

PY - 2011/8

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N2 - Objective: YY1 is a zinc finger transcription factor involved in the regulation of cell growth, development, and differentiation. Although YY1 can regulate human papillomavirusYtype (HPV) viral oncogenes E6 and E7, it remains unknown if YY1 plays a key role in carcinoma progression of HPV-infected cells. Here we sought to determine whether YY1 is upregulated in the cervical cancer tissues and YY1 inhibition contributes to apoptosis of cervical cancer cells, which is at least partly p 53 dependent. Therefore, YY1 can be a potential therapeutic target for cervical cancer treatment by arsenic trioxide (As 2O 3). Materials and Methods: The expression level of YY1 was examined and analyzed by Western blot in pathologically confirmed primary cervical cancer samples, in the adjacent normal samples, as well as in normal cervix samples. The effects of YY1 inhibition by specific small interfering RNA in HeLa cells were determined by Western blot analysis of p 53 level, cell growth curve, colony formation assay, and apoptosis. The contribution of YY1 to As 2O 3-induced p 53 activation and apoptosis was also examined by Western blot and cell cycle analysis. Results: Here we report that the expression level of YY1 is significantly elevated in the primary cancer tissues. In HPV-positive HeLa cells, small interfering RNAYmediated YY1 inhibition induced apoptosis and increased the expression of p 53. Treatment of HeLa cells with As 2O 3, a known antiYcervical cancer agent, reduced both protein and mRNA levels of YY1 in HeLa cells. YY1 knockdown significantly further enhanced As 2O 3- induced apoptosis. Conclusions: These results demonstrated that the expression of YY1 is upregulated in cervical carcinomas and that YY1 plays a critical role in the progression of HPV-positive cervical cancer. In addition, YY1 inhibition induces p 53 activation and apoptosis in HPVinfected HeLa cells. Thus, YY1 is an As 2O 3 target and could serve as a potential drug sensitizer for antiYcervical cancer therapy.

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