Article Text

Download PDFPDF
Microarray Analysis Identifies Differentially Expressed Genes Induced by Human Papillomavirus Type 18 E6 Silencing RNA
  1. Wei Min, PhD*,
  2. Ma Wen-Li, MD, PhD*,
  3. Sun Zhao-Hui, PhD,
  4. Li Ling, PhD*,
  5. Zhang Bao, PhD* and
  6. Zheng Wen-Ling, MD, PhD
  1. *Institute of Molecular Biology, Southern Medical University;
  2. Department of Clinical Laboratory, Guangzhou Liuhuaqiao Hospital; and
  3. Southern China Genomics Research Center, Guangzhou, People's Republic of China.
  1. Address correspondence and reprint requests to Ma Wen-li, Institute of Molecular Biology, Southern Medical University, Guangzhou 510515, People's Republic of China. E-mail: wenli668{at}


The oncoprotein E6 of high-risk human papillomavirus (HPV) types promotes cell proliferation and contributes to carcinogenesis of HPV-positive cervical cancer cells. In this study, we used small interfering RNA (siRNA) technology to silence the E6 gene in HPV-18-transformed human cervical cell line HeLa and determined the effects of E6 gene knockdown on the cell by using microarray-based gene expression profiling coupled with gene functional classification with bioinformatics methods. Silencing RNA prepared by siRNA expression cassettes against HPV-18 E6 gene could significantly inhibit E6 gene expression and induce HeLa cells to apoptosis. The microarray analysis identified 359 differentially expressed genes containing 307 up-regulated and 52 down-regulated genes. We analyzed the gene functions and cellular pathways in detail, including cell cycle-related genes, CCNG1 and p21; apoptosis-related genes, CASP4, CASP6, IGFBP3, and DFFA; ubiquitin proteolysis pathway-related genes, UBE3A and UBE2C; keratinocyte differentiation-related genes, KRT4, KRT6E, and KRT18; and antioncogenes, RECK and VEL. In addition, it can be concluded that cellular apoptosis induced by HPV-18 E6 siRNA mainly depends on the P53 and ubiquitin proteolysis pathway to regulate gene expression, consequently inhibiting cell proliferation and promoting cell apoptosis. Meanwhile, activation of antioncogene and upper regulation of immunization-related genes signified the degression of the malignant extent of tumor cells after E6 inhibition. Our approach, which combines the use of siRNA-mediated gene silencing, microarray screening, and functional classification of differential genes, can be used in functional genomics study to elucidate the role of E6 oncogene in the carcinogenesis of HPV-18 and provide some possible targets for clinical treatment and drug development of cervical cancer.

  • siRNA
  • Microarray
  • HPV
  • E6

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • This work was supported by the Natural Science Foundation of Guangdong Province, China (grant No. D07300239), and the Medical Scientific Research Foundation of Guangdong Province, China (grant No.WSTJJ20071201360103197802270749).