Human papillomavirus infection and expression of ATPase family AAA domain containing 3A, a novel anti-autophagy factor, in uterine cervical cancer

被引:61
作者
Chen, Tai-Chang [2 ,3 ]
Hung, Yao-Ching [4 ,5 ]
Lin, Tze-Yi [6 ]
Chang, Hui-Wen [6 ]
Chiang, I-Ping [6 ]
Chen, Yueh-Ying [7 ]
Chow, Kuan-Chih [1 ]
机构
[1] Natl Chung Hsing Univ, Grad Inst Biomed Sci, Taichung 40227, Taiwan
[2] Natl Taiwan Univ Hosp, Hsin Chu Branch, Dept Obstet & Gynecol, Hsinchu, Taiwan
[3] Chung Hua Univ, Dept Ind Management, Hsinchu, Taiwan
[4] China Med Univ, Coll Med, Taichung, Taiwan
[5] China Med Univ Hosp, Dept Obstet & Gynecol, Taichung, Taiwan
[6] China Med Univ, China Med Univ Hosp, Dept Pathol, Taichung, Taiwan
[7] Taipei Vet Gen Hosp, Su Ao Branch, Dept Lab Med, Ilan, Taiwan
关键词
high risk HPV; ATAD3A; drug resistance; autophagy; prognosis; DIHYDRODIOL DEHYDROGENASE; APOPTOTIC FACTOR; UP-REGULATION; CISPLATIN; OVEREXPRESSION; RESISTANCE; CARCINOMA; NEOPLASIA; GENOTYPE; MARKER;
D O I
10.3892/ijmm.2011.743
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
100103 [病原生物学]; 100218 [急诊医学];
摘要
Our aim was to determine the association of human papillomavirus (HPV) infection with the expression of ATPase family AAA domain containing 3A (ATAD3A), an anti-autophagy factor, in uterine cervical cancer (UCC). The HPV genotype was determined by an Easychip HPV blot assay. ATAD3A expression was determined by immunohistochemical staining. High-risk HPV (hrHPV) was detected in 184 (88.9%) of 207 UCC cases. ATAD3A expression was detected in 164 (79.2%) UCC cases. A significant correlation was found between ATAD3A expression and the presence of hrHPV (p<0.001),FIGO stage (p=0.014), lymph node involvement (p=0.001), c-MET expression (p<0.001), interleukin-8 (p=0.03) and patient survival (p=0.0016). Interestingly, silencing of E6/E7 expression decreased ATAD3A expression and cell survival. Moreover, knockdown of ATAD3A (ATAD3A(kd)) expression or addition of resveratrol, increased cellular autophagy and apoptosis and reduced drug resistance. Resveratrol reduced ATAD3A expression, and increased abrasion of the mitochondrial outer membrane as well as numbers of autophagosomes, the phenomena that were frequently found in ATAD3A(kd) cells. In conclusion, our results show that HPV infection correlates with increased ATAD3A expression and drug resistance in UCC. Persistent HPV infection may stabilize ATAD3A expression to inhibit cell autophagy and apoptosis as well as to increase drug resistance.
引用
收藏
页码:689 / 696
页数:8
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