Knockdown of LMNB1 Inhibits the Proliferation of Lung Adenocarcinoma Cells by Inducing DNA Damage and Cell Senescence
BackgroundLung cancer has considerably high mortality and morbidity rate. Lung adenocarcinoma (LUAD) tissues highly express lamin B1 (LMNB1), compared with normal tissues. In this study, we knocked down LMNB1 in LUAD cells A549 and NCI-1299 to explore the effect of its inhibition on the proliferatio...
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.913740/full |
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| author | Jiangbo Li Zhijia Sun Yingshu Cui Lingmei Qin Fengyun Wu Yufang Li Nan Du Xiaosong Li Xiaosong Li |
| author_facet | Jiangbo Li Zhijia Sun Yingshu Cui Lingmei Qin Fengyun Wu Yufang Li Nan Du Xiaosong Li Xiaosong Li |
| author_sort | Jiangbo Li |
| collection | DOAJ |
| description | BackgroundLung cancer has considerably high mortality and morbidity rate. Lung adenocarcinoma (LUAD) tissues highly express lamin B1 (LMNB1), compared with normal tissues. In this study, we knocked down LMNB1 in LUAD cells A549 and NCI-1299 to explore the effect of its inhibition on the proliferation of cells and the potential mechanism.MethodsUsing bioinformatics methods, we analyzed the specificity of LMNB1 mRNA expression level in LUAD and its effect on prognosis from TCGA data. SiRNAs were used to knock down LMNB1 in the A549 cell line, and the knockdown effect was identified by western blotting and qRT-PCR. Through CCK8 cell proliferation assay, wound healing assay, TRAP, cloning formation Assay, DNase I-TUNEL assay, ATAC-seq, immunofluorescence, FISH, in vivo mouse xenograft studies, etc, we evaluated the influence and mechanism of LMNB1 on LUAD cell line proliferation in vitro and in vivo.ResultsAccording to bioinformatics analysis, LMNB1 is substantially abundant in LUAD tissues and is associated with tumor stage and patient survival (P < 0.05). After silencing LMNB1, the rate of cell growth, wound healing, the number of transwells, and the number of cell colonies all decreased significantly (P < 0.01). With the decreased LMNB1 expression, H3K9me3 protein expression decreases, chromosome accessibility increases, P53, P21, P16 and γ-H2AX protein expression increases, and the number of senescence staining positive cells increases. At the same time, in vivo mouse xenograft experiments showed that the tumor volume of the LMNB1-silenced group was significantly reduced, compared to that of the control group (P < 0.01), and the proliferation biomarker Ki-67 level (P < 0.01) was considerably reduced.ConclusionsOverexpression of LMNB1 in LUAD cells is significant, which has excellent potential to be an indicator for evaluating the clinical prognosis of LUAD patients and a target for precise treatment. |
| first_indexed | 2024-04-13T22:06:44Z |
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| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T22:06:44Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-ede76826351e45e0ab6d5ea029bde9fb2022-12-22T02:27:56ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-05-011210.3389/fonc.2022.913740913740Knockdown of LMNB1 Inhibits the Proliferation of Lung Adenocarcinoma Cells by Inducing DNA Damage and Cell SenescenceJiangbo Li0Zhijia Sun1Yingshu Cui2Lingmei Qin3Fengyun Wu4Yufang Li5Nan Du6Xiaosong Li7Xiaosong Li8Department of Biology, Beijing Institute of Biotechnology, Beijing, ChinaMedical School of Chinese People's Liberation Army (PLA), Chinese People's Liberation Army General Hospital, Beijing, ChinaMedical School of Chinese People's Liberation Army (PLA), Chinese People's Liberation Army General Hospital, Beijing, ChinaDepartment of Biology, Beijing Institute of Biotechnology, Beijing, ChinaCollege of Life Sciences, Capital Normal University, Beijing, ChinaCollege of Life Sciences, Capital Normal University, Beijing, ChinaDepartment of Oncology, Fourth Medical Center of Chinese PLA General Hospital, Chinese People's Liberation Army General Hospital, Beijing, ChinaDepartment of Oncology, Fourth Medical Center of Chinese PLA General Hospital, Chinese People's Liberation Army General Hospital, Beijing, ChinaDepartment of Oncology, Seventh Medical Center of Chinese PLA General Hospital, Chinese People's Liberation Army General Hospital, Beijing, ChinaBackgroundLung cancer has considerably high mortality and morbidity rate. Lung adenocarcinoma (LUAD) tissues highly express lamin B1 (LMNB1), compared with normal tissues. In this study, we knocked down LMNB1 in LUAD cells A549 and NCI-1299 to explore the effect of its inhibition on the proliferation of cells and the potential mechanism.MethodsUsing bioinformatics methods, we analyzed the specificity of LMNB1 mRNA expression level in LUAD and its effect on prognosis from TCGA data. SiRNAs were used to knock down LMNB1 in the A549 cell line, and the knockdown effect was identified by western blotting and qRT-PCR. Through CCK8 cell proliferation assay, wound healing assay, TRAP, cloning formation Assay, DNase I-TUNEL assay, ATAC-seq, immunofluorescence, FISH, in vivo mouse xenograft studies, etc, we evaluated the influence and mechanism of LMNB1 on LUAD cell line proliferation in vitro and in vivo.ResultsAccording to bioinformatics analysis, LMNB1 is substantially abundant in LUAD tissues and is associated with tumor stage and patient survival (P < 0.05). After silencing LMNB1, the rate of cell growth, wound healing, the number of transwells, and the number of cell colonies all decreased significantly (P < 0.01). With the decreased LMNB1 expression, H3K9me3 protein expression decreases, chromosome accessibility increases, P53, P21, P16 and γ-H2AX protein expression increases, and the number of senescence staining positive cells increases. At the same time, in vivo mouse xenograft experiments showed that the tumor volume of the LMNB1-silenced group was significantly reduced, compared to that of the control group (P < 0.01), and the proliferation biomarker Ki-67 level (P < 0.01) was considerably reduced.ConclusionsOverexpression of LMNB1 in LUAD cells is significant, which has excellent potential to be an indicator for evaluating the clinical prognosis of LUAD patients and a target for precise treatment.https://www.frontiersin.org/articles/10.3389/fonc.2022.913740/fullLMNB1LUADchromosome accessibilitytelomerecell senescence |
| spellingShingle | Jiangbo Li Zhijia Sun Yingshu Cui Lingmei Qin Fengyun Wu Yufang Li Nan Du Xiaosong Li Xiaosong Li Knockdown of LMNB1 Inhibits the Proliferation of Lung Adenocarcinoma Cells by Inducing DNA Damage and Cell Senescence Frontiers in Oncology LMNB1 LUAD chromosome accessibility telomere cell senescence |
| title | Knockdown of LMNB1 Inhibits the Proliferation of Lung Adenocarcinoma Cells by Inducing DNA Damage and Cell Senescence |
| title_full | Knockdown of LMNB1 Inhibits the Proliferation of Lung Adenocarcinoma Cells by Inducing DNA Damage and Cell Senescence |
| title_fullStr | Knockdown of LMNB1 Inhibits the Proliferation of Lung Adenocarcinoma Cells by Inducing DNA Damage and Cell Senescence |
| title_full_unstemmed | Knockdown of LMNB1 Inhibits the Proliferation of Lung Adenocarcinoma Cells by Inducing DNA Damage and Cell Senescence |
| title_short | Knockdown of LMNB1 Inhibits the Proliferation of Lung Adenocarcinoma Cells by Inducing DNA Damage and Cell Senescence |
| title_sort | knockdown of lmnb1 inhibits the proliferation of lung adenocarcinoma cells by inducing dna damage and cell senescence |
| topic | LMNB1 LUAD chromosome accessibility telomere cell senescence |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.913740/full |
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