Abstract
Although long noncoding RNAs (lncRNAs) have been implicated in the progression of prostate cancer (PCa), the functional roles of many of these molecules, especially in metastasis, remain poorly understood. To identify novel lncRNAs linked to PCa malignant phenotypes, we analyzed the differences in lncRNA expression between the highly metastatic PCa cell line (PC-3 M-1E8) and the poorly metastatic PCa cell line (PC-3 M-2B4) using transcriptome sequencing. This differential expression was confirmed by RT-qPCR, which showed that the lnc-ALX1-2 gene cluster (including lnc-ALX1-2:5, lnc-ALX1-2:7, lnc-ALX1-2:10) was significantly upregulated in PC-3 M-1E8 cells. Functional studies demonstrated that knockdown of the lnc-ALX1-2 gene cluster suppressed proliferation, migration, and invasion in PC-3 M-1E8 cells, with lnc-ALX1-2:10 showing the most prominent effect. Transcriptome analysis further revealed that lnc-ALX1-2:10 knockdown altered the expression of 194 genes related to both proliferation and migration. RT-qPCR and Western blot validated that lnc-ALX1-2:10 knockdown downregulated pro-tumorigenic factors (CCNE1, PDGFRA, ANGPT4) and EMT markers (N-cadherin, Snail, Vimentin), while upregulating ITGAL and E-cadherin. In vivo, lnc-ALX1-2:10 knockdown obviously decreased tumor volume but had no effect on mouse body weight, and molecular analysis of xenograft tumors confirmed consistent expression changes of key proteins as in vitro. Collectively, our findings identify lnc-ALX1-2:10 as a novel lncRNA that promotes aggressive phenotypes in PCa, highlighting its potential as a therapeutic target for metastatic disease.
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Data availability
The datasets generated by Forevergen Biosciences are available in NCBI with the ID: PRJNA753212(https://www.ncbi.nlm.nih.gov/bioproject/PRJNA753212).
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Funding
This research was supported by Natural Science Foundation of Xiamen, China (Project No. 3502Z202373098, Xinjun Wang), Natural Science Foundation of Fujian Province (Grant Nos. 2023J011592, Xinjun Wang and 2024J011333 Guangcheng Luo), and Major Project (2024GZL-ZD03, Guangcheng Luo) and and Youth Project (2024GZL-QN103, Zhangqun Li) under the Xiamen Health High-Quality Development Science and Technology Program.
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Conceptualization, Funding acquisition: LGC, WXJ and LZQ; Data curation, Formal analysis, Validation: ZQ and LZQ; Methodology: ZB; Investigation: WXQ; Project administration, Writing - original draft: WXJ; Resources, Software, Visualization: BY; Supervision, Writing - review & editing: LGC.
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Animal experiment was approved by the committee of Guangzhou Forevergen Biosciences (Guangzhou, China, approval number: IACUC-G16057). We confirm that all methods were performed in accordance with the relevant guidelines and regulations. The study is reported in accordance with ARRIVE guidelines.
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Wang, X., Zong, Q., Bu, Y. et al. lnc-ALX1-2:10 is a novel regulator that enhances proliferation, migration and invasion in prostate cancer cells. Sci Rep (2026). https://doi.org/10.1038/s41598-026-42299-0
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DOI: https://doi.org/10.1038/s41598-026-42299-0
