MiR-196b-5p activates NF-κB signaling in non-small cell lung cancer by directly targeting NFKBIA
Background: Our recent study found that QKI-5 regulated miRNA, miR-196b-5p, promotes non-small cell lung cancer (NSCLC) progression by directly targeting GATA6, TSPAN12 and FAS. However, the biological functions of miR-196b-5p in NSCLC progression and metastasis still remain elusive. Methods: Cell p...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523323001419 |
| _version_ | 1797685295595913216 |
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| author | Wangyu Zhu Yun Yu Yuxin Ye Xinyue Tu Yan Zhang Tao Wu Lianli Ni Xiangjie Huang Yumin Wang Ri Cui |
| author_facet | Wangyu Zhu Yun Yu Yuxin Ye Xinyue Tu Yan Zhang Tao Wu Lianli Ni Xiangjie Huang Yumin Wang Ri Cui |
| author_sort | Wangyu Zhu |
| collection | DOAJ |
| description | Background: Our recent study found that QKI-5 regulated miRNA, miR-196b-5p, promotes non-small cell lung cancer (NSCLC) progression by directly targeting GATA6, TSPAN12 and FAS. However, the biological functions of miR-196b-5p in NSCLC progression and metastasis still remain elusive. Methods: Cell proliferation, migration, colony formation, cell cycle assays were used to investigate cellular phenotypic changes. Quantitative real-time PCR (qRT-PCR) and western blot analyses were used to measure expressions of relative gene and protein. Interaction between QKI-5 and miR-196b-5p was determined by RNA immunoprecipitation (RIP) assay. Luciferase reporter assay was used to determine direct binding between miR-196b-5p and NFKBIA 3′-UTR. ELISA assay was used to measure secreted IL6 proteins. Mice xenograft model was used to assess the functions of NFKBIA on in vivo tumor growth. Results: We demonstrated that the miR-196b-5p facilitates lung cancer cell proliferation, migration, colony formation, and cell cycle by directly targeting NFKBIA, a negative regulator of NFκB signaling. Knocking down NFKBIA increases IL6 mediated phosphorylation of signal transducer and activator of transcription 3 (STAT3) to promote lung cancer cell growth by activating NFκB signaling. The expression of NFKBIA was significantly downregulated in NSCLC tissue samples, and was negatively correlated with the expression miR-196b-5p. In addition, we found that downregulated QKI-5 expression was associated with the elevated miR-224 expression in NSCLC. Conclusions: Our findings indicated that the miR-224/QKI-5/miR-196b-5p/NFKBIA signaling pathway might play important functions in the progression of NSCLC, and suggested that targeting this pathway might be an effective therapeutic strategy in treating NSCLC. |
| first_indexed | 2024-03-12T00:42:08Z |
| format | Article |
| id | doaj.art-5227be1b30cb4591a3cd689db2e739e1 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-03-12T00:42:08Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-5227be1b30cb4591a3cd689db2e739e12023-09-15T04:39:24ZengElsevierTranslational Oncology1936-52332023-11-0137101755MiR-196b-5p activates NF-κB signaling in non-small cell lung cancer by directly targeting NFKBIAWangyu Zhu0Yun Yu1Yuxin Ye2Xinyue Tu3Yan Zhang4Tao Wu5Lianli Ni6Xiangjie Huang7Yumin Wang8Ri Cui9Cellular and Molecular Biology Laboratory, Affiliated Zhoushan Hospital of Wenzhou Medical University, Zhoushan, Zhejiang 316020, China; Cancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaCellular and Molecular Biology Laboratory, Affiliated Zhoushan Hospital of Wenzhou Medical University, Zhoushan, Zhejiang 316020, China; Cancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaCancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaCancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaCancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, ChinaCancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaCancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaCancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaKey Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Corresponding author at: Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, ChinaCellular and Molecular Biology Laboratory, Affiliated Zhoushan Hospital of Wenzhou Medical University, Zhoushan, Zhejiang 316020, China; Cancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Corresponding author: Cancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.Background: Our recent study found that QKI-5 regulated miRNA, miR-196b-5p, promotes non-small cell lung cancer (NSCLC) progression by directly targeting GATA6, TSPAN12 and FAS. However, the biological functions of miR-196b-5p in NSCLC progression and metastasis still remain elusive. Methods: Cell proliferation, migration, colony formation, cell cycle assays were used to investigate cellular phenotypic changes. Quantitative real-time PCR (qRT-PCR) and western blot analyses were used to measure expressions of relative gene and protein. Interaction between QKI-5 and miR-196b-5p was determined by RNA immunoprecipitation (RIP) assay. Luciferase reporter assay was used to determine direct binding between miR-196b-5p and NFKBIA 3′-UTR. ELISA assay was used to measure secreted IL6 proteins. Mice xenograft model was used to assess the functions of NFKBIA on in vivo tumor growth. Results: We demonstrated that the miR-196b-5p facilitates lung cancer cell proliferation, migration, colony formation, and cell cycle by directly targeting NFKBIA, a negative regulator of NFκB signaling. Knocking down NFKBIA increases IL6 mediated phosphorylation of signal transducer and activator of transcription 3 (STAT3) to promote lung cancer cell growth by activating NFκB signaling. The expression of NFKBIA was significantly downregulated in NSCLC tissue samples, and was negatively correlated with the expression miR-196b-5p. In addition, we found that downregulated QKI-5 expression was associated with the elevated miR-224 expression in NSCLC. Conclusions: Our findings indicated that the miR-224/QKI-5/miR-196b-5p/NFKBIA signaling pathway might play important functions in the progression of NSCLC, and suggested that targeting this pathway might be an effective therapeutic strategy in treating NSCLC.http://www.sciencedirect.com/science/article/pii/S1936523323001419miR-196b-5pNSCLCNFKBIANF-κBSTAT3IL-6 |
| spellingShingle | Wangyu Zhu Yun Yu Yuxin Ye Xinyue Tu Yan Zhang Tao Wu Lianli Ni Xiangjie Huang Yumin Wang Ri Cui MiR-196b-5p activates NF-κB signaling in non-small cell lung cancer by directly targeting NFKBIA Translational Oncology miR-196b-5p NSCLC NFKBIA NF-κB STAT3 IL-6 |
| title | MiR-196b-5p activates NF-κB signaling in non-small cell lung cancer by directly targeting NFKBIA |
| title_full | MiR-196b-5p activates NF-κB signaling in non-small cell lung cancer by directly targeting NFKBIA |
| title_fullStr | MiR-196b-5p activates NF-κB signaling in non-small cell lung cancer by directly targeting NFKBIA |
| title_full_unstemmed | MiR-196b-5p activates NF-κB signaling in non-small cell lung cancer by directly targeting NFKBIA |
| title_short | MiR-196b-5p activates NF-κB signaling in non-small cell lung cancer by directly targeting NFKBIA |
| title_sort | mir 196b 5p activates nf κb signaling in non small cell lung cancer by directly targeting nfkbia |
| topic | miR-196b-5p NSCLC NFKBIA NF-κB STAT3 IL-6 |
| url | http://www.sciencedirect.com/science/article/pii/S1936523323001419 |
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