Splicing inhibition mediated by reduced splicing factors and helicases is associated with the cellular response of lung cancer cells to cisplatin
Lung cancer’s mortality is predominantly linked to post-chemotherapy recurrence, driven by the reactivation of dormant cancer cells. Despite the critical role of these reactivated cells in cancer recurrence and metastasis, the molecular mechanisms governing their therapeutic selection remain poorly...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037023005147 |
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| author | Lujuan Wang Na Yin Wenhua Shi Yaohuan Xie Junqi Yi Ziying Tang Jingqun Tang Juanjuan Xiang |
| author_facet | Lujuan Wang Na Yin Wenhua Shi Yaohuan Xie Junqi Yi Ziying Tang Jingqun Tang Juanjuan Xiang |
| author_sort | Lujuan Wang |
| collection | DOAJ |
| description | Lung cancer’s mortality is predominantly linked to post-chemotherapy recurrence, driven by the reactivation of dormant cancer cells. Despite the critical role of these reactivated cells in cancer recurrence and metastasis, the molecular mechanisms governing their therapeutic selection remain poorly understood. In this study, we conducted an integrative analysis by combining PacBio single molecule real-time (SMRT) sequencing with short reads Illumina RNA-seq. Our study revealed that cisplatin-induced dormant and reactivated cancer cells exhibited a noteworthy reduction in gene transcripts and alternative splicing events. Particularly, the differential alternative splicing events were found to be overlapping with the differentially expression genes and enriched in genes related to cell cycle and cell division. Utilizing ENCORI database and correlation analysis, we identified key splicing factors, including SRSF7, SRSF3, PRPF8, and HNRNPC, as well as RNA helicase such as EIF4A3, DDX39A, DDX11, and BRIP1, which were associated with the observed reduction in alternative splicing and subsequent decrease in gene expression. Our study demonstrated that lung cancer cells reduce gene transcripts through diminished alternative splicing events mediated by specific splicing factors and RNA helicase in response to the chemotherapeutic stress. These findings provide insights into the molecular mechanisms underlying the therapeutic selection and reactivation of dormant cancer cells. This discovery opens a potential avenue for the development of therapeutic strategies aimed at preventing cancer recurrence following chemotherapy. |
| first_indexed | 2024-03-08T15:53:09Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-03-08T15:53:09Z |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-e8279a0c7a1b4c57a967f38da39ad1f52024-01-09T04:04:21ZengElsevierComputational and Structural Biotechnology Journal2001-03702024-12-0123648658Splicing inhibition mediated by reduced splicing factors and helicases is associated with the cellular response of lung cancer cells to cisplatinLujuan Wang0Na Yin1Wenhua Shi2Yaohuan Xie3Junqi Yi4Ziying Tang5Jingqun Tang6Juanjuan Xiang7Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Changsha, Hunan 410011, China; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan 410011, China; NHC Key Laboratory of Carcinogenesis and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410013, ChinaCancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan 410011, China; NHC Key Laboratory of Carcinogenesis and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410013, ChinaCancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan 410011, China; NHC Key Laboratory of Carcinogenesis and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410013, ChinaCancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan 410011, China; NHC Key Laboratory of Carcinogenesis and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410013, ChinaHunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, The Second Xiangya Hospital, Changsha, Hunan 410011, China; Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, ChinaHunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, The Second Xiangya Hospital, Changsha, Hunan 410011, China; Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, ChinaHunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, The Second Xiangya Hospital, Changsha, Hunan 410011, China; Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Correspondence to: The Second Xiangya Hospital, Changsha, Hunan 410011, China.Hunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, The Second Xiangya Hospital, Changsha, Hunan 410011, China; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan 410011, China; NHC Key Laboratory of Carcinogenesis and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Correspondence to: The Second Xiangya Hospital, Changsha, Hunan 410011, China.Lung cancer’s mortality is predominantly linked to post-chemotherapy recurrence, driven by the reactivation of dormant cancer cells. Despite the critical role of these reactivated cells in cancer recurrence and metastasis, the molecular mechanisms governing their therapeutic selection remain poorly understood. In this study, we conducted an integrative analysis by combining PacBio single molecule real-time (SMRT) sequencing with short reads Illumina RNA-seq. Our study revealed that cisplatin-induced dormant and reactivated cancer cells exhibited a noteworthy reduction in gene transcripts and alternative splicing events. Particularly, the differential alternative splicing events were found to be overlapping with the differentially expression genes and enriched in genes related to cell cycle and cell division. Utilizing ENCORI database and correlation analysis, we identified key splicing factors, including SRSF7, SRSF3, PRPF8, and HNRNPC, as well as RNA helicase such as EIF4A3, DDX39A, DDX11, and BRIP1, which were associated with the observed reduction in alternative splicing and subsequent decrease in gene expression. Our study demonstrated that lung cancer cells reduce gene transcripts through diminished alternative splicing events mediated by specific splicing factors and RNA helicase in response to the chemotherapeutic stress. These findings provide insights into the molecular mechanisms underlying the therapeutic selection and reactivation of dormant cancer cells. This discovery opens a potential avenue for the development of therapeutic strategies aimed at preventing cancer recurrence following chemotherapy.http://www.sciencedirect.com/science/article/pii/S2001037023005147Cell dormancyChemotherapyLung adenocarcinoma cellsSplicing inhibition |
| spellingShingle | Lujuan Wang Na Yin Wenhua Shi Yaohuan Xie Junqi Yi Ziying Tang Jingqun Tang Juanjuan Xiang Splicing inhibition mediated by reduced splicing factors and helicases is associated with the cellular response of lung cancer cells to cisplatin Computational and Structural Biotechnology Journal Cell dormancy Chemotherapy Lung adenocarcinoma cells Splicing inhibition |
| title | Splicing inhibition mediated by reduced splicing factors and helicases is associated with the cellular response of lung cancer cells to cisplatin |
| title_full | Splicing inhibition mediated by reduced splicing factors and helicases is associated with the cellular response of lung cancer cells to cisplatin |
| title_fullStr | Splicing inhibition mediated by reduced splicing factors and helicases is associated with the cellular response of lung cancer cells to cisplatin |
| title_full_unstemmed | Splicing inhibition mediated by reduced splicing factors and helicases is associated with the cellular response of lung cancer cells to cisplatin |
| title_short | Splicing inhibition mediated by reduced splicing factors and helicases is associated with the cellular response of lung cancer cells to cisplatin |
| title_sort | splicing inhibition mediated by reduced splicing factors and helicases is associated with the cellular response of lung cancer cells to cisplatin |
| topic | Cell dormancy Chemotherapy Lung adenocarcinoma cells Splicing inhibition |
| url | http://www.sciencedirect.com/science/article/pii/S2001037023005147 |
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