Examination of the functions and mechanism of KCP in mediating paclitaxel resistance in cervical squamous carcinoma cells
ObjectiveTo evaluate the mechanism of Kielin/chordin-like protein (KCP) in the resistance of cervical cancer cells to paclitaxel.MethodA cervical squamous carcinoma cell line (SiHa) with KCP knockout was constructed and treated with paclitaxel. Key cell functions were assessed by colony formation as...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1550032/full |
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| author | Yue He Jian-Qing Xu Jing-Jing Zhang Zhen-You Liu Chen Ji Yang Liu Yun-Fan Wang Ming Wang Yu-Mei Wu Yan Wang |
| author_facet | Yue He Jian-Qing Xu Jing-Jing Zhang Zhen-You Liu Chen Ji Yang Liu Yun-Fan Wang Ming Wang Yu-Mei Wu Yan Wang |
| author_sort | Yue He |
| collection | DOAJ |
| description | ObjectiveTo evaluate the mechanism of Kielin/chordin-like protein (KCP) in the resistance of cervical cancer cells to paclitaxel.MethodA cervical squamous carcinoma cell line (SiHa) with KCP knockout was constructed and treated with paclitaxel. Key cell functions were assessed by colony formation assay, measurement of cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and FACS-based detection of apoptosis. The downstream mechanism of KCP-mediated resistance to paclitaxel was then examined using human gene chip detection and IPA bioinformatics analysis, and qPCR analysis was used to validate its downstream genes.Results①Functional studies of SiHa cells showed that KCP knockout (sgRNA) inhibited colony formation and proliferation of SiHa cells in the presence of paclitaxel (p<0.05). ②Using a whole human genome microarray, a total of 491 differentially expressed genes were identified in KCP knockout versus the NC SiHa cells. IPA-based bioinformatics analysis of upstream regulators showed that SPI1 was strongly activated and that SPI1 inhibited CCND1 and activated PML and CEBPA, which is consistent with results from gene chip analysis showing CCND1, PML, and CEBPA expression after KCP knockout. ③A total of 30 differentially expressed genes associated with tumor cell proliferation were identified by gene microarray and IPA analyses. The changes in the aforementioned genes after KCP knockout were verified by qPCR, and SERPINB3 and CEBPA expression were significantly lower and higher, respectively, compared to in the control group.ConclusionKCP increased resistance of cervical cancer to paclitaxel by enhancing cell proliferation and colony formation. We observed that KCP could act positively on the downstream gene SERPINB3 and negatively on the downstream gene CEBPA to affect the resistance of cervical carcinoma cells to paclitaxel. |
| format | Article |
| id | doaj-art-cffc2c62095b40b5a11f69aa3eddb1b8 |
| institution | DOAJ |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-cffc2c62095b40b5a11f69aa3eddb1b82025-08-20T03:06:35ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-04-011510.3389/fonc.2025.15500321550032Examination of the functions and mechanism of KCP in mediating paclitaxel resistance in cervical squamous carcinoma cellsYue HeJian-Qing XuJing-Jing ZhangZhen-You LiuChen JiYang LiuYun-Fan WangMing WangYu-Mei WuYan WangObjectiveTo evaluate the mechanism of Kielin/chordin-like protein (KCP) in the resistance of cervical cancer cells to paclitaxel.MethodA cervical squamous carcinoma cell line (SiHa) with KCP knockout was constructed and treated with paclitaxel. Key cell functions were assessed by colony formation assay, measurement of cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and FACS-based detection of apoptosis. The downstream mechanism of KCP-mediated resistance to paclitaxel was then examined using human gene chip detection and IPA bioinformatics analysis, and qPCR analysis was used to validate its downstream genes.Results①Functional studies of SiHa cells showed that KCP knockout (sgRNA) inhibited colony formation and proliferation of SiHa cells in the presence of paclitaxel (p<0.05). ②Using a whole human genome microarray, a total of 491 differentially expressed genes were identified in KCP knockout versus the NC SiHa cells. IPA-based bioinformatics analysis of upstream regulators showed that SPI1 was strongly activated and that SPI1 inhibited CCND1 and activated PML and CEBPA, which is consistent with results from gene chip analysis showing CCND1, PML, and CEBPA expression after KCP knockout. ③A total of 30 differentially expressed genes associated with tumor cell proliferation were identified by gene microarray and IPA analyses. The changes in the aforementioned genes after KCP knockout were verified by qPCR, and SERPINB3 and CEBPA expression were significantly lower and higher, respectively, compared to in the control group.ConclusionKCP increased resistance of cervical cancer to paclitaxel by enhancing cell proliferation and colony formation. We observed that KCP could act positively on the downstream gene SERPINB3 and negatively on the downstream gene CEBPA to affect the resistance of cervical carcinoma cells to paclitaxel.https://www.frontiersin.org/articles/10.3389/fonc.2025.1550032/fullKielin/chordin-like proteinpaclitaxel resistancecervical squamous cell carcinomamechanismfunctions |
| spellingShingle | Yue He Jian-Qing Xu Jing-Jing Zhang Zhen-You Liu Chen Ji Yang Liu Yun-Fan Wang Ming Wang Yu-Mei Wu Yan Wang Examination of the functions and mechanism of KCP in mediating paclitaxel resistance in cervical squamous carcinoma cells Frontiers in Oncology Kielin/chordin-like protein paclitaxel resistance cervical squamous cell carcinoma mechanism functions |
| title | Examination of the functions and mechanism of KCP in mediating paclitaxel resistance in cervical squamous carcinoma cells |
| title_full | Examination of the functions and mechanism of KCP in mediating paclitaxel resistance in cervical squamous carcinoma cells |
| title_fullStr | Examination of the functions and mechanism of KCP in mediating paclitaxel resistance in cervical squamous carcinoma cells |
| title_full_unstemmed | Examination of the functions and mechanism of KCP in mediating paclitaxel resistance in cervical squamous carcinoma cells |
| title_short | Examination of the functions and mechanism of KCP in mediating paclitaxel resistance in cervical squamous carcinoma cells |
| title_sort | examination of the functions and mechanism of kcp in mediating paclitaxel resistance in cervical squamous carcinoma cells |
| topic | Kielin/chordin-like protein paclitaxel resistance cervical squamous cell carcinoma mechanism functions |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1550032/full |
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