TNIK regulates actin cytoskeleton morphology via Rho/ROCK/LIMK1 pathway in lung adenocarcinoma A549 cells
Objective To investigate the molecular mechanism of TNIK regulating actin cytoskeleton morphology in lung adenocarcinoma A549 cells, and determine its effects on the proliferation and apoptosis of the cancer cells when combined with mitosis-targeted drug. Methods RNA sequencing data were profiled to...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | zho |
| Published: |
Editorial Office of Journal of Army Medical University
2023-04-01
|
| Series: | 陆军军医大学学报 |
| Subjects: | |
| Online Access: | http://aammt.tmmu.edu.cn/html/202210102.htm |
| _version_ | 1797845661932060672 |
|---|---|
| author | SUN Xuehua SUN Xuehua ZHANG Lian ZHANG Lian ZHANG Chundong ZHANG Chundong CHEN Quan |
| author_facet | SUN Xuehua SUN Xuehua ZHANG Lian ZHANG Lian ZHANG Chundong ZHANG Chundong CHEN Quan |
| author_sort | SUN Xuehua |
| collection | DOAJ |
| description | Objective To investigate the molecular mechanism of TNIK regulating actin cytoskeleton morphology in lung adenocarcinoma A549 cells, and determine its effects on the proliferation and apoptosis of the cancer cells when combined with mitosis-targeted drug. Methods RNA sequencing data were profiled to screen differentially expressed genes in the A549 cells with TNIK stable knockdown, and the expression of genes related to actin cytoskeleton assembly was subsequently detected. RT-PCR, Western blotting, and double immunofluorescence staining were preformed to analyze the molecular mechanism of TNIK regulating the assembly of actin-microtubule cytoskeleton system. Moreover, A549 cells with TNIK knockdown were treated with targeted antimitotic chemotherapeutic agent, paclitaxel, to observe the growth and apoptosis of the cancer cells. Results RNA-seq showed that the differentially expressed genes after TNIK knockdown were closely associated with mitotic progression. Further analysis revealed that TNIK knockdown significantly inhibited the expression of Rho pathway related genes including RhoA/B, ROCK1/2 and LIMK1 at the transcriptional level (P < 0.01), but had no obvious effect on the expression of Rac and CDC42 pathway related genes. Immunofluorescence assay indicated that TNIK knockdown resulted in abnormal mitosis and morphology in actin cytoskeleton system. As compared with the control cells, paclitaxel treatment decreased the proliferation (P < 0.01) while improved the apoptotic rate (P < 0.01) in TNIK knockdown cells. Conclusion TNIK regulates the morphology of actin-microtubule cytoskeleton system in lung adenocarcinoma A549 cells through the Rho/ROCK/LIMK1 pathway, and TNIK knockdown can enhance the efficiency of mitosis-targeted chemotherapeutic drug.
|
| first_indexed | 2024-04-09T17:42:38Z |
| format | Article |
| id | doaj.art-3dc229f1c3ec47cc9d250c9cc5502e4f |
| institution | Directory Open Access Journal |
| issn | 2097-0927 |
| language | zho |
| last_indexed | 2024-04-09T17:42:38Z |
| publishDate | 2023-04-01 |
| publisher | Editorial Office of Journal of Army Medical University |
| record_format | Article |
| series | 陆军军医大学学报 |
| spelling | doaj.art-3dc229f1c3ec47cc9d250c9cc5502e4f2023-04-17T01:26:23ZzhoEditorial Office of Journal of Army Medical University陆军军医大学学报2097-09272023-04-0145765966610.16016/j.2097-0927.202210102TNIK regulates actin cytoskeleton morphology via Rho/ROCK/LIMK1 pathway in lung adenocarcinoma A549 cellsSUN Xuehua0SUN Xuehua1 ZHANG Lian2 ZHANG Lian3ZHANG Chundong4ZHANG Chundong5CHEN Quan6Molecular Medicine and Cancer Research Center, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, ChinaDepartment of Immunology, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, ChinaMolecular Medicine and Cancer Research Center, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, ChinaDepartment of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, ChinaMolecular Medicine and Cancer Research Center, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, ChinaDepartment of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, ChinaDepartment of Immunology, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, ChinaObjective To investigate the molecular mechanism of TNIK regulating actin cytoskeleton morphology in lung adenocarcinoma A549 cells, and determine its effects on the proliferation and apoptosis of the cancer cells when combined with mitosis-targeted drug. Methods RNA sequencing data were profiled to screen differentially expressed genes in the A549 cells with TNIK stable knockdown, and the expression of genes related to actin cytoskeleton assembly was subsequently detected. RT-PCR, Western blotting, and double immunofluorescence staining were preformed to analyze the molecular mechanism of TNIK regulating the assembly of actin-microtubule cytoskeleton system. Moreover, A549 cells with TNIK knockdown were treated with targeted antimitotic chemotherapeutic agent, paclitaxel, to observe the growth and apoptosis of the cancer cells. Results RNA-seq showed that the differentially expressed genes after TNIK knockdown were closely associated with mitotic progression. Further analysis revealed that TNIK knockdown significantly inhibited the expression of Rho pathway related genes including RhoA/B, ROCK1/2 and LIMK1 at the transcriptional level (P < 0.01), but had no obvious effect on the expression of Rac and CDC42 pathway related genes. Immunofluorescence assay indicated that TNIK knockdown resulted in abnormal mitosis and morphology in actin cytoskeleton system. As compared with the control cells, paclitaxel treatment decreased the proliferation (P < 0.01) while improved the apoptotic rate (P < 0.01) in TNIK knockdown cells. Conclusion TNIK regulates the morphology of actin-microtubule cytoskeleton system in lung adenocarcinoma A549 cells through the Rho/ROCK/LIMK1 pathway, and TNIK knockdown can enhance the efficiency of mitosis-targeted chemotherapeutic drug. http://aammt.tmmu.edu.cn/html/202210102.htmlung adenocarcinoma cellsactin cytoskeletonmicrotubule cytoskeletonchemotherapytnik |
| spellingShingle | SUN Xuehua SUN Xuehua ZHANG Lian ZHANG Lian ZHANG Chundong ZHANG Chundong CHEN Quan TNIK regulates actin cytoskeleton morphology via Rho/ROCK/LIMK1 pathway in lung adenocarcinoma A549 cells 陆军军医大学学报 lung adenocarcinoma cells actin cytoskeleton microtubule cytoskeleton chemotherapy tnik |
| title | TNIK regulates actin cytoskeleton morphology via Rho/ROCK/LIMK1 pathway in lung adenocarcinoma A549 cells |
| title_full | TNIK regulates actin cytoskeleton morphology via Rho/ROCK/LIMK1 pathway in lung adenocarcinoma A549 cells |
| title_fullStr | TNIK regulates actin cytoskeleton morphology via Rho/ROCK/LIMK1 pathway in lung adenocarcinoma A549 cells |
| title_full_unstemmed | TNIK regulates actin cytoskeleton morphology via Rho/ROCK/LIMK1 pathway in lung adenocarcinoma A549 cells |
| title_short | TNIK regulates actin cytoskeleton morphology via Rho/ROCK/LIMK1 pathway in lung adenocarcinoma A549 cells |
| title_sort | tnik regulates actin cytoskeleton morphology via rho rock limk1 pathway in lung adenocarcinoma a549 cells |
| topic | lung adenocarcinoma cells actin cytoskeleton microtubule cytoskeleton chemotherapy tnik |
| url | http://aammt.tmmu.edu.cn/html/202210102.htm |
| work_keys_str_mv | AT sunxuehua tnikregulatesactincytoskeletonmorphologyviarhorocklimk1pathwayinlungadenocarcinomaa549cells AT sunxuehua tnikregulatesactincytoskeletonmorphologyviarhorocklimk1pathwayinlungadenocarcinomaa549cells AT zhanglian tnikregulatesactincytoskeletonmorphologyviarhorocklimk1pathwayinlungadenocarcinomaa549cells AT zhanglian tnikregulatesactincytoskeletonmorphologyviarhorocklimk1pathwayinlungadenocarcinomaa549cells AT zhangchundong tnikregulatesactincytoskeletonmorphologyviarhorocklimk1pathwayinlungadenocarcinomaa549cells AT zhangchundong tnikregulatesactincytoskeletonmorphologyviarhorocklimk1pathwayinlungadenocarcinomaa549cells AT chenquan tnikregulatesactincytoskeletonmorphologyviarhorocklimk1pathwayinlungadenocarcinomaa549cells |