LncRNA PTTG3P promotes tumorigenesis and metastasis of NSCLC by binding with ILF3 to maintain mRNA stability and form a positive feedback loop with E2F1

Wang, Jing; He, Xuezhi; Yao, Qing; Wang, Chan; Lu, Xiyi; Wang, Rong; Miao, Dengshun

doi:10.7150/ijbs.81738

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Theranostics

International Journal of Medical Sciences

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Int J Biol Sci 2023; 19(13):4291-4310. doi:10.7150/ijbs.81738 This issue Cite

Research Paper

LncRNA PTTG3P promotes tumorigenesis and metastasis of NSCLC by binding with ILF3 to maintain mRNA stability and form a positive feedback loop with E2F1

Jing Wang^1#, Xuezhi He^1#, Qing Yao^2#, Chan Wang¹, Xiyi Lu³, Rong Wang¹, Dengshun Miao^1✉

1. Department of Human Anatomy, Histology and Embryology, The Research Center for Bone and Stem Cells, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
2. Department of Endocrinology, Changzhou Second People's Hospital Affiliated Nanjing Medical University, No.29 Xinglong Road, 213003 Changzhou, Jiangsu, People's Republic of China.
3. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, Jiangsu, China.
#These authors have contributed equally to this work.

Citation:

Wang J, He X, Yao Q, Wang C, Lu X, Wang R, Miao D. LncRNA PTTG3P promotes tumorigenesis and metastasis of NSCLC by binding with ILF3 to maintain mRNA stability and form a positive feedback loop with E2F1. Int J Biol Sci 2023; 19(13):4291-4310. doi:10.7150/ijbs.81738. https://www.ijbs.com/v19p4291.htm

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Abstract

Non-small cell lung cancer (NSCLC) is a highly lethal disease worldwide. We found the pseudogene-derived lncRNA PTTG3P is upregulated in NSCLC and associated with larger tumor size, advanced staging, and poor prognosis. This study investigated the oncogenic roles and mechanisms of PTTG3P in NSCLC. We demonstrate that PTTG3P promoted NSCLC cell proliferation, migration, tumorigenesis, and metastasis while inhibiting apoptosis in vitro and in vivo. Mechanistically, PTTG3P formed an RNA-protein complex with ILF3 to maintain MAP2K6 and E2F1 mRNA stability, two oncogenic factors involved in NSCLC progression. RNA-seq revealed MAP2K6 and E2F1 were downregulated upon PTTG3P knockdown. RIP and RNA stability assays showed PTTG3P/ILF3 interaction stabilized MAP2K6 and E2F1 transcripts. Interestingly, E2F1 transcriptionally upregulated PTTG3P by binding its promoter, forming a positive feedback loop. Knockdown of E2F1 or PTTG3P attenuated their mutual regulatory effects on cell growth and migration. Thus, a PTTG3P/ILF3/E2F1 axis enhances oncogene expression to promote NSCLC pathogenesis. Our study reveals PTTG3P exerts oncogenic functions in NSCLC via mRNA stabilization and a feedback loop, highlighting its potential as a prognostic biomarker and therapeutic target.

Keywords: long non-coding RNA, PTTG3P, ILF3, non-small cell lung cancer, E2F1.

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APA

Wang, J., He, X., Yao, Q., Wang, C., Lu, X., Wang, R., Miao, D. (2023). LncRNA PTTG3P promotes tumorigenesis and metastasis of NSCLC by binding with ILF3 to maintain mRNA stability and form a positive feedback loop with E2F1. International Journal of Biological Sciences, 19(13), 4291-4310. https://doi.org/10.7150/ijbs.81738.

ACS

Wang, J.; He, X.; Yao, Q.; Wang, C.; Lu, X.; Wang, R.; Miao, D. LncRNA PTTG3P promotes tumorigenesis and metastasis of NSCLC by binding with ILF3 to maintain mRNA stability and form a positive feedback loop with E2F1. Int. J. Biol. Sci. 2023, 19 (13), 4291-4310. DOI: 10.7150/ijbs.81738.

NLM

CSE

Wang J, He X, Yao Q, Wang C, Lu X, Wang R, Miao D. 2023. LncRNA PTTG3P promotes tumorigenesis and metastasis of NSCLC by binding with ILF3 to maintain mRNA stability and form a positive feedback loop with E2F1. Int J Biol Sci. 19(13):4291-4310.

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