HPV16 E7 inhibits HBD2 expression by down-regulation of ASK1-p38 MAPK pathway in cervical cancer
Abstract Background Recent researches indicated a down-regulation of Human beta-defensin2 (HBD2) expression in cervical cancer cells, but the mechanism and clinical significance is not clear yet. Methods In this paper, based on the data from the TCGA database, the bioinformatics analysis provided by...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-04-01
|
| Series: | Virology Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12985-025-02731-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850181775006892032 |
|---|---|
| author | Juanjuan Liao Shanshan Deng Bowen Shi Meizhen Wang Yingying Yin Yanli Cao Renping Liu Xiaotian Huang Lixia Jiang Qiaofa Shi |
| author_facet | Juanjuan Liao Shanshan Deng Bowen Shi Meizhen Wang Yingying Yin Yanli Cao Renping Liu Xiaotian Huang Lixia Jiang Qiaofa Shi |
| author_sort | Juanjuan Liao |
| collection | DOAJ |
| description | Abstract Background Recent researches indicated a down-regulation of Human beta-defensin2 (HBD2) expression in cervical cancer cells, but the mechanism and clinical significance is not clear yet. Methods In this paper, based on the data from the TCGA database, the bioinformatics analysis provided by the UALCAN server was used. The HBD2 mRNA levels were tested with RT-qPCR in cells and protein concentration in cell cultural supernatant was assayed with ELISA. When the gene of Human papillomavirus type 16 E7 oncoprotein (HPV16 E7) overexpression or knockdown, the protein expression of ASK1 and p38 MAPK was detected by Western blot. Results The bioinformatics analysis results implied that mRNA levels of HBD2 in cervical cancer were lower obviously than healthy people. HBD2 mRNA levels and protein in CaSki and SiHa cells increased obviously under the condition of HPV16 E7 gene silence. However, HBD2 mRNA and protein levels decreased significantly in C33A and CaCo2 cells not only under the conditions of treatment with HPV16 E7 gene overexpression, but also the inhibition of ASK1-p38 MAPK pathway by SB-203580 or GS-4997, or shRNA expression plasmid of ASK1 transefction. Moreover, p-ASK1(Thr845), the activity forming protein of ASK1, and p-p38, decreased in C33A and CaCo2 cells accompanied with HPV16 E7 overexpression, while p-ASK1(Ser966) protein, an inhibitory forming protein kept in a same stable levels. The completely opposite patterns of the protein expression in ASK1-p38 MAPK pathway were obtained in CaSki and SiHa cells transfected with HPV16 E7 siRNA sequence. Interestingly, statistical higher levels of phosphorylated p38 and cellular apoptosis rates, were found in SiHa cells exposed in Anisomycin than in DMSO solution. And increased HBD2 protein concentration in cell cultural supernatant and decreased cell survial rates, were confirmed in CaSki and SiHa cells treatment with Anisomycin, at the same time. Conclusions Our results implied that HPV16 E7 suppresses HBD2 expression via the inhibition of the ASK1-p38 MAPK signaling pathway, and this mechanism might be a key way of anti-tumor effect of Anisomycin. This study provided a novel insight into the expression and regulation mechanism of HBD2 in tumors and offered a possible therapeutic strategy by using defensins for cervical cancer in future. |
| format | Article |
| id | doaj-art-fe0140dae1524f6dba7fe8f0f898d7f9 |
| institution | OA Journals |
| issn | 1743-422X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Virology Journal |
| spelling | doaj-art-fe0140dae1524f6dba7fe8f0f898d7f92025-08-20T02:17:49ZengBMCVirology Journal1743-422X2025-04-0122111410.1186/s12985-025-02731-9HPV16 E7 inhibits HBD2 expression by down-regulation of ASK1-p38 MAPK pathway in cervical cancerJuanjuan Liao0Shanshan Deng1Bowen Shi2Meizhen Wang3Yingying Yin4Yanli Cao5Renping Liu6Xiaotian Huang7Lixia Jiang8Qiaofa Shi9Department of Medical Microbiology & Immunology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang UniversityDepartment of Medical Microbiology & Immunology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang UniversityThe First Clinical Medical College, Nanchang Universitythe hospital of Nanchang University, Nanchang Universitythe hospital of Nanchang University, Nanchang UniversityDepartment of Medical Microbiology & Immunology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang UniversityDepartment of Medical Microbiology & Immunology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang UniversityDepartment of Medical Microbiology & Immunology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang UniversityDepartment of Laboratory Medicine, First Affiliated Hospital of Gannan Medical UniversityDepartment of Medical Microbiology & Immunology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang UniversityAbstract Background Recent researches indicated a down-regulation of Human beta-defensin2 (HBD2) expression in cervical cancer cells, but the mechanism and clinical significance is not clear yet. Methods In this paper, based on the data from the TCGA database, the bioinformatics analysis provided by the UALCAN server was used. The HBD2 mRNA levels were tested with RT-qPCR in cells and protein concentration in cell cultural supernatant was assayed with ELISA. When the gene of Human papillomavirus type 16 E7 oncoprotein (HPV16 E7) overexpression or knockdown, the protein expression of ASK1 and p38 MAPK was detected by Western blot. Results The bioinformatics analysis results implied that mRNA levels of HBD2 in cervical cancer were lower obviously than healthy people. HBD2 mRNA levels and protein in CaSki and SiHa cells increased obviously under the condition of HPV16 E7 gene silence. However, HBD2 mRNA and protein levels decreased significantly in C33A and CaCo2 cells not only under the conditions of treatment with HPV16 E7 gene overexpression, but also the inhibition of ASK1-p38 MAPK pathway by SB-203580 or GS-4997, or shRNA expression plasmid of ASK1 transefction. Moreover, p-ASK1(Thr845), the activity forming protein of ASK1, and p-p38, decreased in C33A and CaCo2 cells accompanied with HPV16 E7 overexpression, while p-ASK1(Ser966) protein, an inhibitory forming protein kept in a same stable levels. The completely opposite patterns of the protein expression in ASK1-p38 MAPK pathway were obtained in CaSki and SiHa cells transfected with HPV16 E7 siRNA sequence. Interestingly, statistical higher levels of phosphorylated p38 and cellular apoptosis rates, were found in SiHa cells exposed in Anisomycin than in DMSO solution. And increased HBD2 protein concentration in cell cultural supernatant and decreased cell survial rates, were confirmed in CaSki and SiHa cells treatment with Anisomycin, at the same time. Conclusions Our results implied that HPV16 E7 suppresses HBD2 expression via the inhibition of the ASK1-p38 MAPK signaling pathway, and this mechanism might be a key way of anti-tumor effect of Anisomycin. This study provided a novel insight into the expression and regulation mechanism of HBD2 in tumors and offered a possible therapeutic strategy by using defensins for cervical cancer in future.https://doi.org/10.1186/s12985-025-02731-9Human beta-defensin-2Cervical cancerHPV16ApoptosisAnisomycin |
| spellingShingle | Juanjuan Liao Shanshan Deng Bowen Shi Meizhen Wang Yingying Yin Yanli Cao Renping Liu Xiaotian Huang Lixia Jiang Qiaofa Shi HPV16 E7 inhibits HBD2 expression by down-regulation of ASK1-p38 MAPK pathway in cervical cancer Virology Journal Human beta-defensin-2 Cervical cancer HPV16 Apoptosis Anisomycin |
| title | HPV16 E7 inhibits HBD2 expression by down-regulation of ASK1-p38 MAPK pathway in cervical cancer |
| title_full | HPV16 E7 inhibits HBD2 expression by down-regulation of ASK1-p38 MAPK pathway in cervical cancer |
| title_fullStr | HPV16 E7 inhibits HBD2 expression by down-regulation of ASK1-p38 MAPK pathway in cervical cancer |
| title_full_unstemmed | HPV16 E7 inhibits HBD2 expression by down-regulation of ASK1-p38 MAPK pathway in cervical cancer |
| title_short | HPV16 E7 inhibits HBD2 expression by down-regulation of ASK1-p38 MAPK pathway in cervical cancer |
| title_sort | hpv16 e7 inhibits hbd2 expression by down regulation of ask1 p38 mapk pathway in cervical cancer |
| topic | Human beta-defensin-2 Cervical cancer HPV16 Apoptosis Anisomycin |
| url | https://doi.org/10.1186/s12985-025-02731-9 |
| work_keys_str_mv | AT juanjuanliao hpv16e7inhibitshbd2expressionbydownregulationofask1p38mapkpathwayincervicalcancer AT shanshandeng hpv16e7inhibitshbd2expressionbydownregulationofask1p38mapkpathwayincervicalcancer AT bowenshi hpv16e7inhibitshbd2expressionbydownregulationofask1p38mapkpathwayincervicalcancer AT meizhenwang hpv16e7inhibitshbd2expressionbydownregulationofask1p38mapkpathwayincervicalcancer AT yingyingyin hpv16e7inhibitshbd2expressionbydownregulationofask1p38mapkpathwayincervicalcancer AT yanlicao hpv16e7inhibitshbd2expressionbydownregulationofask1p38mapkpathwayincervicalcancer AT renpingliu hpv16e7inhibitshbd2expressionbydownregulationofask1p38mapkpathwayincervicalcancer AT xiaotianhuang hpv16e7inhibitshbd2expressionbydownregulationofask1p38mapkpathwayincervicalcancer AT lixiajiang hpv16e7inhibitshbd2expressionbydownregulationofask1p38mapkpathwayincervicalcancer AT qiaofashi hpv16e7inhibitshbd2expressionbydownregulationofask1p38mapkpathwayincervicalcancer |