New insights into the function and mechanisms of piRNA PMLCPIR in promoting PM2.5-induced lung cancer
Introduction: Extensive studies have established the correlation between long-term PM2.5 exposure and lung cancer, yet the mechanisms underlying this association remain poorly understood. PIWI-interacting RNAs (piRNAs), a novel category of small non-coding RNAs, serve important roles in various dise...
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Elsevier
2025-07-01
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| Series: | Journal of Advanced Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2090123224003722 |
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| author | Lin Xu Wanli Ma Xiaoyu Huo Jiao Luo Ruoxi Li Xiaoxiao Zhu Xiangbin Kong Kunming Zhao Yuan Jin Meihua Zhang Xianshu Li Ling Wang Wei Han Dianke Yu |
| author_facet | Lin Xu Wanli Ma Xiaoyu Huo Jiao Luo Ruoxi Li Xiaoxiao Zhu Xiangbin Kong Kunming Zhao Yuan Jin Meihua Zhang Xianshu Li Ling Wang Wei Han Dianke Yu |
| author_sort | Lin Xu |
| collection | DOAJ |
| description | Introduction: Extensive studies have established the correlation between long-term PM2.5 exposure and lung cancer, yet the mechanisms underlying this association remain poorly understood. PIWI-interacting RNAs (piRNAs), a novel category of small non-coding RNAs, serve important roles in various diseases. However, their biological function and mechanism in PM2.5-induced lung cancer have not been thoroughly investigated. Objectives: We aimed to explore the oncogenic role of piRNA in lung cancer induced by PM2.5 exposure, as well as the underlying mechanisms. Methods: We conducted a PM2.5-induced human lung epithelial cell malignant transformation model. Human samples were used to further verify the finding. In vitro proliferation, migration, and invasion assays were performed to study the function of piRNA. RNA-sequencing was used to elucidate the the mechanisms of how piRNA mediates cell functions. PiRNA pull-down and computational docking analysis were conducted to identify proteins that binding to piRNA. In vivo experiments were used to explore whether inhibition of PMLCPIR could have a therapeutic effect on lung cancer. Results: We identified a new up-regulated piRNA, termed PM2.5-induced lung cancer up-regulation piRNA (PMLCPIR), which promotes the proliferation of PM2.5-transformed cells and lung cancer cells. RNA sequencing revealed ITGB1 as a downstream target of PMLCPIR. Importantly, PMLCPIR binds to nucleolin (NCL) and increases the expression of its target gene, ITGB1, thereby activating PI3K/AKT signaling. The inhibition of PMLCPIR could promote apoptosis in lung cancer cells and enhance their chemosensitivity to anti-tumor drugs. Conclusion: We systematically identified the alterations of piRNA expression profiles in the PM2.5-induced malignant transformation model. Then, PMLCPIR was recognized as a novel oncogenic piRNA in PM2.5-induced lung cancer. Mechanically, PMLCPIR binds to NCL, enhancing ITGB1 expression and activating the ontogenetic PI3K/AKT signaling, potentially contributing to lung cancer progression. This study provides novel insights into the revelation of a new epigenetic regulator in PM2.5-induced lung cancer. |
| format | Article |
| id | doaj-art-6d734e756f56463aa2fcf314e5e6d845 |
| institution | Kabale University |
| issn | 2090-1232 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
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| series | Journal of Advanced Research |
| spelling | doaj-art-6d734e756f56463aa2fcf314e5e6d8452025-08-20T03:47:16ZengElsevierJournal of Advanced Research2090-12322025-07-017365967010.1016/j.jare.2024.08.029New insights into the function and mechanisms of piRNA PMLCPIR in promoting PM2.5-induced lung cancerLin Xu0Wanli Ma1Xiaoyu Huo2Jiao Luo3Ruoxi Li4Xiaoxiao Zhu5Xiangbin Kong6Kunming Zhao7Yuan Jin8Meihua Zhang9Xianshu Li10Ling Wang11Wei Han12Dianke Yu13Key Laboratory of Materal & Fetal Medicine of National Health Commission of China, Maternal and Child Health Care Hospital of Shandong Province Affiliated to Qingdao University, Jinan, China; School of Public Health, Qingdao University, Qingdao, ChinaSchool of Public Health, Qingdao University, Qingdao, ChinaSchool of Public Health, Qingdao University, Qingdao, ChinaSchool of Public Health, Qingdao University, Qingdao, ChinaSchool of Public Health, Qingdao University, Qingdao, ChinaSchool of Public Health, Qingdao University, Qingdao, ChinaSchool of Public Health, Qingdao University, Qingdao, ChinaSchool of Public Health, Qingdao University, Qingdao, ChinaSchool of Public Health, Qingdao University, Qingdao, ChinaKey Laboratory of Materal & Fetal Medicine of National Health Commission of China, Maternal and Child Health Care Hospital of Shandong Province Affiliated to Qingdao University, Jinan, ChinaKey Laboratory of Materal & Fetal Medicine of National Health Commission of China, Maternal and Child Health Care Hospital of Shandong Province Affiliated to Qingdao University, Jinan, ChinaClinical Laboratory, Children’s Hospital Affiliated to Shandong University, Jinan, China; Corresponding authors at: Clinical Laboratory, Children’s Hospital Affiliated to Shandong University, 23976 Jing-Shi Road, Jinan, Shandong 250022, China.Department of Pulmonary and Critical Care Medicine, Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, Qingdao, China; Corresponding author at: Department of Pulmonary and Critical Care Medicine, Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, No. 1 Jiaozhou Road, Qingdao, Shandong 266011, China.School of Public Health, Qingdao University, Qingdao, China; Corresponding author at: School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao, Shandong 266071, China.Introduction: Extensive studies have established the correlation between long-term PM2.5 exposure and lung cancer, yet the mechanisms underlying this association remain poorly understood. PIWI-interacting RNAs (piRNAs), a novel category of small non-coding RNAs, serve important roles in various diseases. However, their biological function and mechanism in PM2.5-induced lung cancer have not been thoroughly investigated. Objectives: We aimed to explore the oncogenic role of piRNA in lung cancer induced by PM2.5 exposure, as well as the underlying mechanisms. Methods: We conducted a PM2.5-induced human lung epithelial cell malignant transformation model. Human samples were used to further verify the finding. In vitro proliferation, migration, and invasion assays were performed to study the function of piRNA. RNA-sequencing was used to elucidate the the mechanisms of how piRNA mediates cell functions. PiRNA pull-down and computational docking analysis were conducted to identify proteins that binding to piRNA. In vivo experiments were used to explore whether inhibition of PMLCPIR could have a therapeutic effect on lung cancer. Results: We identified a new up-regulated piRNA, termed PM2.5-induced lung cancer up-regulation piRNA (PMLCPIR), which promotes the proliferation of PM2.5-transformed cells and lung cancer cells. RNA sequencing revealed ITGB1 as a downstream target of PMLCPIR. Importantly, PMLCPIR binds to nucleolin (NCL) and increases the expression of its target gene, ITGB1, thereby activating PI3K/AKT signaling. The inhibition of PMLCPIR could promote apoptosis in lung cancer cells and enhance their chemosensitivity to anti-tumor drugs. Conclusion: We systematically identified the alterations of piRNA expression profiles in the PM2.5-induced malignant transformation model. Then, PMLCPIR was recognized as a novel oncogenic piRNA in PM2.5-induced lung cancer. Mechanically, PMLCPIR binds to NCL, enhancing ITGB1 expression and activating the ontogenetic PI3K/AKT signaling, potentially contributing to lung cancer progression. This study provides novel insights into the revelation of a new epigenetic regulator in PM2.5-induced lung cancer.http://www.sciencedirect.com/science/article/pii/S2090123224003722PM2.5Lung cancerMalignant transformationpiRNAITGB1-PI3K-AKT axis |
| spellingShingle | Lin Xu Wanli Ma Xiaoyu Huo Jiao Luo Ruoxi Li Xiaoxiao Zhu Xiangbin Kong Kunming Zhao Yuan Jin Meihua Zhang Xianshu Li Ling Wang Wei Han Dianke Yu New insights into the function and mechanisms of piRNA PMLCPIR in promoting PM2.5-induced lung cancer Journal of Advanced Research PM2.5 Lung cancer Malignant transformation piRNA ITGB1-PI3K-AKT axis |
| title | New insights into the function and mechanisms of piRNA PMLCPIR in promoting PM2.5-induced lung cancer |
| title_full | New insights into the function and mechanisms of piRNA PMLCPIR in promoting PM2.5-induced lung cancer |
| title_fullStr | New insights into the function and mechanisms of piRNA PMLCPIR in promoting PM2.5-induced lung cancer |
| title_full_unstemmed | New insights into the function and mechanisms of piRNA PMLCPIR in promoting PM2.5-induced lung cancer |
| title_short | New insights into the function and mechanisms of piRNA PMLCPIR in promoting PM2.5-induced lung cancer |
| title_sort | new insights into the function and mechanisms of pirna pmlcpir in promoting pm2 5 induced lung cancer |
| topic | PM2.5 Lung cancer Malignant transformation piRNA ITGB1-PI3K-AKT axis |
| url | http://www.sciencedirect.com/science/article/pii/S2090123224003722 |
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