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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2015.1
- 수록면
- 210 - 216 (7page)
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Objective This study was to identify small inhibitory RNAs (siRNAs) that are effective in inhibiting growth of cervical cancer cell lines harboring human papilloma virus (HPV) and to examine how siRNAs interact with interferon beta (IFN-β) and thimerosal.
Methods The HPV18-positive HeLa and C-4I cell lines were used. Four types of siRNAs were designed according to their target (both E6 and E7 vs. E6 only) and sizes (21- vs. 27-nucleotides); Ex-18E6/21, Ex-18E6/27, Sp-18E6/21, and Sp-18E6/27. Each siRNA-transfected cells were cultured with or without IFN-b and thimerosal and their viability was measured.
Results The viabilities of HPV18-positive tumor cells were reduced by 21- and 27-nucleotide siRNAs in proportion to the siRNA concentrations. Of the two types of siRNAs, the 27-nucleotide siRNA constructs showed greater inhibitory efficacy. Sp-18E6 siRNAs, which selectively downregulates E6 protein only, were more effective than the E6- and E7-targeting Ex-18E6 siRNAs. siRNAs and IFN-β showed the synergistic effect to inhibit HeLa cell survival and the effect was proportional to both siRNA and IFN-β concentrations. Thimerosal in the presence of siRNA exerted a dose-dependent inhibition of C-4I cell survival. Finally, co-treatment with siRNA, IFN-β, and thimerosal induced the most profound decrease in the viability of both cell lines.
Conclusion Long (27-nucleotides) siRNAs targeting E6–E7 mRNAs effectively reduce the viability of HPV18-positive cervical cancer cells and show the synergistic effect in combination with IFN-b and thimerosal. It is necessary to find the rational design of siRNAs and effective co-factors to eradicate particular cervical cancer.
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참고문헌 (23)
참고문헌 신청
Amarzguioui M. / 2003 / Tolerance for mutations and chemical modifications in a siRNA / Nucleic Acids Res 31 : 589 ~ 595
Bosch FX. / 2007 / The epidemiology of human papillomavirus infection and cervical cancer / Dis Markers 23 : 213 ~ 227
Chiantore MV. / 2012 / Interferon-β induces cellular senescence in cutaneous human papilloma virus-transformed human keratinocytes by affecting p53 transactivating activity
DeFilippis RA. / 2003 / Endogenous human papillomavirus E6 and E7 proteins differentially regulate proliferation, senescence, and apoptosis in HeLa cervical carcinoma cells
Elbashir SM. / 2001 / Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells / Nature 411 : 494 ~ 498
Bosch FX. / 2007 / The epidemiology of human papillomavirus infection and cervical cancer / Dis Markers 23 : 213 ~ 227
Chiantore MV. / 2012 / Interferon-β induces cellular senescence in cutaneous human papilloma virus-transformed human keratinocytes by affecting p53 transactivating activity
DeFilippis RA. / 2003 / Endogenous human papillomavirus E6 and E7 proteins differentially regulate proliferation, senescence, and apoptosis in HeLa cervical carcinoma cells
Elbashir SM. / 2001 / Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells / Nature 411 : 494 ~ 498
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