PMID- 36502630 OWN - NLM STAT- MEDLINE DCOM- 20230201 LR - 20231213 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 640 DP - 2023 Jan 15 TI - Newly identified lncRNA-45 promotes breast cancer metastasis through activating the mTOR signaling pathway. PG - 40-49 LID - S0006-291X(22)01656-4 [pii] LID - 10.1016/j.bbrc.2022.11.099 [doi] AB - BACKGROUND: Metastasis, a complex multi-stage process, is the primary cause of breast cancer-related death. Unfortunately, the molecular mechanisms underlying tumor metastasis have not been fully elucidated thus far. Long noncoding RNAs (lncRNAs) dictate the behaviours of tumor cells via multiple signaling pathways, resulting in tumor cell migration and invasion, as well as all stages of cancer progression. LncRNAs function as regulators in shaping cellular activities directly through influencing key genes involved in biological processes of the tumor, and representing promising novel targets in cancer diagnosis and therapy. We therefore sought to define the correlations between lncRNA expression and breast cancer metastasis, especially to investigate the functional pathway underlying lncRNA-mediated tumor invasion and metastasis process. RESULTS: In this study, we compared the lncRNA transcriptome profiles between primary breast cancer 4T1 cells and high metastatic 4T1-LG12 cells. We found that many differently expressed lncRNAs greatly correlated to the metastatic propensity of 4T1-LG12 cells, particularly lncRNA-45, a new lncRNA without functional annotations, which was found to be the most upregulated lncRNA transcribed by an internal region within the regulatory associated with protein of mechanistic target of rapamycin kinase (mTOR) complex 1 (Rptor) gene. LncRNA-45 was uncovered to be involved in the epithelial-to-mesenchymal transition process of breast cancer cells, as evidenced by the observation that lncRNA-45 knockdown significantly suppressed the invasive capability of parental 4T1-LG12 cells. Molecular mechanistic investigation showed that reduced activity of mTORC1-associated pathway led to a decrease of total ribosomal protein S6 kinase, polypeptide 1 (S6K1) content and enhancement of autophagy, consequently compromising the metastatic propensity in lncRNA-45 knockdown cells. CONCLUSIONS: Overall, our experiments uncovered that the newly identified lncRNA-45 played a regulatory role in breast cancer cell metastasis. CI - Copyright (c) 2022. Published by Elsevier Inc. FAU - Qiu, Jiahuang AU - Qiu J AD - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China. FAU - Guo, Yifan AU - Guo Y AD - Department of Clinical Laboratory, Peking University People's Hospital, Beijing, 100044, China. FAU - Wang, Shunhao AU - Wang S AD - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China. FAU - Ren, Quanzhong AU - Ren Q AD - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China. FAU - Dong, Zheng AU - Dong Z AD - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China. FAU - Gao, Ming AU - Gao M AD - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China. FAU - Ma, Juan AU - Ma J AD - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address: juanm@rcees.ac.cn. FAU - Chen, Shuguang AU - Chen S AD - Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. FAU - Liu, Sijin AU - Liu S AD - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221202 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1) RN - EC 2.7.1.1 (MTOR protein, human) RN - 0 (RNA, Long Noncoding) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Female MH - Humans MH - *Breast Neoplasms/metabolism/pathology MH - Cell Line, Tumor MH - Cell Movement/genetics MH - Cell Proliferation/genetics MH - Epithelial-Mesenchymal Transition/genetics MH - Gene Expression Regulation, Neoplastic MH - *Mechanistic Target of Rapamycin Complex 1/metabolism MH - Neoplasm Metastasis MH - *RNA, Long Noncoding/genetics/metabolism MH - Signal Transduction/genetics MH - TOR Serine-Threonine Kinases/metabolism MH - Melanoma, Cutaneous Malignant OTO - NOTNLM OT - Breast cancer OT - LncRNA OT - Tumor metastasis OT - mTOR pathway COIS- Declaration of competing interest There is no potential conflict of interests to disclose. EDAT- 2022/12/12 06:00 MHDA- 2023/01/11 06:00 CRDT- 2022/12/11 18:15 PHST- 2022/10/15 00:00 [received] PHST- 2022/11/30 00:00 [accepted] PHST- 2022/12/12 06:00 [pubmed] PHST- 2023/01/11 06:00 [medline] PHST- 2022/12/11 18:15 [entrez] AID - S0006-291X(22)01656-4 [pii] AID - 10.1016/j.bbrc.2022.11.099 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2023 Jan 15;640:40-49. doi: 10.1016/j.bbrc.2022.11.099. Epub 2022 Dec 2.