Downregulation of KIAA1199 by miR‐486‐5p suppresses tumorigenesis in lung cancer
Abstract Lung cancer is the primary cause of death among cancer patients in China, among which nonsmall cell lung cancer (NSCLC) makes up the great majority. Hence, it is imperative to identify the biomarkers and mechanisms involved in NSCLC oncogenesis. Our present research found that KIAA1199 expr...
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| Format: | Article |
| Language: | English |
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Wiley
2020-08-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.3210 |
| _version_ | 1829114160819994624 |
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| author | Anqi Wang Jianjie Zhu Juan Li Wenwen Du Yang Zhang Tingting Cai Ting Liu Yulong Fu Yuanyuan Zeng Zeyi Liu Jian‐an Huang |
| author_facet | Anqi Wang Jianjie Zhu Juan Li Wenwen Du Yang Zhang Tingting Cai Ting Liu Yulong Fu Yuanyuan Zeng Zeyi Liu Jian‐an Huang |
| author_sort | Anqi Wang |
| collection | DOAJ |
| description | Abstract Lung cancer is the primary cause of death among cancer patients in China, among which nonsmall cell lung cancer (NSCLC) makes up the great majority. Hence, it is imperative to identify the biomarkers and mechanisms involved in NSCLC oncogenesis. Our present research found that KIAA1199 expression was significantly increased in NSCLC and closely related to cell proliferation, motility, and poor prognosis. We demonstrated that knockdown of KIAA1199 reduced NSCLC cell growth and motility in vitro whereas overexpression of KIAA1199 had the opposite effect. Inhibition of KIAA1199 significantly suppressed tumor growth in mouse NSCLC xenograft models. Mechanistically, as an epidermal growth factor receptor (EGFR)‐binding protein, KIAA1199 promotes EGFR signaling and regulates EGFR‐dependent Src, Erk, and Akt phosphorylation, as well as downstream kinases in the EGF‐mediated EMT pathway. We demonstrated that KIAA1199 can function as a direct binding target for miR‐486‐5p and that miR‐486‐5p overexpression can attenuate proliferation and migration of NSCLC cells via regulating the EGFR signaling pathways. To conclude, our results defined KIAA1199 as an oncogenic protein that promotes cancer cell proliferation and migration by regulating EGF‐mediated signaling pathways. This study provided new insight into NSCLC oncogenesis, which could lead to the development of innovative therapeutic plans for NSCLC. |
| first_indexed | 2024-12-12T15:50:24Z |
| format | Article |
| id | doaj.art-ef826be4e26f48818540dc11c6376e18 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-12-12T15:50:24Z |
| publishDate | 2020-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-ef826be4e26f48818540dc11c6376e182022-12-22T00:19:39ZengWileyCancer Medicine2045-76342020-08-019155570558610.1002/cam4.3210Downregulation of KIAA1199 by miR‐486‐5p suppresses tumorigenesis in lung cancerAnqi Wang0Jianjie Zhu1Juan Li2Wenwen Du3Yang Zhang4Tingting Cai5Ting Liu6Yulong Fu7Yuanyuan Zeng8Zeyi Liu9Jian‐an Huang10Department of Respiratory Medicine the First Affiliated Hospital of Soochow University Suzhou ChinaDepartment of Respiratory Medicine the First Affiliated Hospital of Soochow University Suzhou ChinaDepartment of Respiratory Medicine the First Affiliated Hospital of Soochow University Suzhou ChinaDepartment of Respiratory Medicine the First Affiliated Hospital of Soochow University Suzhou ChinaDepartment of Respiratory Medicine the First Affiliated Hospital of Soochow University Suzhou ChinaDepartment of Respiratory Medicine the First Affiliated Hospital of Soochow University Suzhou ChinaDepartment of Respiratory Medicine the First Affiliated Hospital of Soochow University Suzhou ChinaDepartment of Respiratory Medicine the First Affiliated Hospital of Soochow University Suzhou ChinaDepartment of Respiratory Medicine the First Affiliated Hospital of Soochow University Suzhou ChinaDepartment of Respiratory Medicine the First Affiliated Hospital of Soochow University Suzhou ChinaDepartment of Respiratory Medicine the First Affiliated Hospital of Soochow University Suzhou ChinaAbstract Lung cancer is the primary cause of death among cancer patients in China, among which nonsmall cell lung cancer (NSCLC) makes up the great majority. Hence, it is imperative to identify the biomarkers and mechanisms involved in NSCLC oncogenesis. Our present research found that KIAA1199 expression was significantly increased in NSCLC and closely related to cell proliferation, motility, and poor prognosis. We demonstrated that knockdown of KIAA1199 reduced NSCLC cell growth and motility in vitro whereas overexpression of KIAA1199 had the opposite effect. Inhibition of KIAA1199 significantly suppressed tumor growth in mouse NSCLC xenograft models. Mechanistically, as an epidermal growth factor receptor (EGFR)‐binding protein, KIAA1199 promotes EGFR signaling and regulates EGFR‐dependent Src, Erk, and Akt phosphorylation, as well as downstream kinases in the EGF‐mediated EMT pathway. We demonstrated that KIAA1199 can function as a direct binding target for miR‐486‐5p and that miR‐486‐5p overexpression can attenuate proliferation and migration of NSCLC cells via regulating the EGFR signaling pathways. To conclude, our results defined KIAA1199 as an oncogenic protein that promotes cancer cell proliferation and migration by regulating EGF‐mediated signaling pathways. This study provided new insight into NSCLC oncogenesis, which could lead to the development of innovative therapeutic plans for NSCLC.https://doi.org/10.1002/cam4.3210cell motilitycell proliferationKIAA1199microRNAmiR‐486‐5pNon‐small cell lung cancer (NSCLC) |
| spellingShingle | Anqi Wang Jianjie Zhu Juan Li Wenwen Du Yang Zhang Tingting Cai Ting Liu Yulong Fu Yuanyuan Zeng Zeyi Liu Jian‐an Huang Downregulation of KIAA1199 by miR‐486‐5p suppresses tumorigenesis in lung cancer Cancer Medicine cell motility cell proliferation KIAA1199 microRNA miR‐486‐5p Non‐small cell lung cancer (NSCLC) |
| title | Downregulation of KIAA1199 by miR‐486‐5p suppresses tumorigenesis in lung cancer |
| title_full | Downregulation of KIAA1199 by miR‐486‐5p suppresses tumorigenesis in lung cancer |
| title_fullStr | Downregulation of KIAA1199 by miR‐486‐5p suppresses tumorigenesis in lung cancer |
| title_full_unstemmed | Downregulation of KIAA1199 by miR‐486‐5p suppresses tumorigenesis in lung cancer |
| title_short | Downregulation of KIAA1199 by miR‐486‐5p suppresses tumorigenesis in lung cancer |
| title_sort | downregulation of kiaa1199 by mir 486 5p suppresses tumorigenesis in lung cancer |
| topic | cell motility cell proliferation KIAA1199 microRNA miR‐486‐5p Non‐small cell lung cancer (NSCLC) |
| url | https://doi.org/10.1002/cam4.3210 |
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