PMID- 37310074 OWN - NLM STAT- MEDLINE DCOM- 20231027 LR - 20231112 IS - 1607-8438 (Electronic) IS - 0300-8207 (Linking) VI - 64 IP - 6 DP - 2023 Nov TI - Knockdown of LncRNA DICER1-AS1 arrests the cell cycle, inhibits cell proliferation, and induces cell apoptosis by regulating CDC5L nuclear transfer in osteosarcoma. PG - 519-531 LID - 10.1080/03008207.2023.2223289 [doi] AB - BACKGROUND: DICER1-AS1 is reported to promote the progression and disturb the cell cycle in osteosarcoma; however, its mechanism has rarely been studied. MATERIALS AND METHODS: DICER1-AS1 expression levels were evaluated by qPCR and fluorescence in situ hybridization (FISH). The total, nuclear, and cytosolic levels of CDC5L were measured by western blotting and immunofluorescence (IF). Cell proliferation, apoptosis, and cell cycle analyses were conducted using the colony formation, CCK-8 assay, terminal transferase-mediated UTP nick end-labeling kit (TUNEL) assay, and flow cytometry. Levels of cell proliferation-, cell cycle-, and cell apoptosis-related proteins were determined by western blotting. RNA immunoprecipitation (RIP) and RNA pull-down assays were conducted to evaluate the relationship between DICER1-AS1 and CDC5L. RESULTS: LncRNA DICER1-AS1 was highly expressed in samples of osteosarcoma tissue and in osteosarcoma cell lines. DICER1-AS1 knockdown inhibited cell proliferation, promoted cell apoptosis, and disturbed the cell cycle. Moreover, DICER1-AS1 was found to bind with CDC5L, and knockdown of DICER-AS1 inhibited the nuclear transfer of CDC5L. DICER1-AS1 knockdown also reversed the effects of CDC5L overexpression on cell proliferation, apoptosis, and the cell cycle. Moreover, CDC5L inhibition suppressed cell proliferation, promoted cell apoptosis, and disturbed the cell cycle, and those effects were further enhanced by DICER1-AS1 knockdown. Finally, DICER1-AS knockdown inhibited tumor growth and proliferation, and promoted cell apoptosis in vivo. CONCLUSION: LncRNA DICER1-AS1 knockdown inhibits the nuclear transfer of CDC5L protein, arrests the cell cycle, and induces apoptosis to suppress the development of osteosarcoma. Our results suggest a novel target (DICER1-AS1) for treatment of osteosarcoma. FAU - Fu, Laihua AU - Fu L AD - National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China. FAU - Xu, Songfeng AU - Xu S AD - National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China. FAU - Zhou, Yang AU - Zhou Y AD - National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China. FAU - Huang, Jingyang AU - Huang J AD - National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China. FAU - Qiu, Jin AU - Qiu J AD - National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China. FAU - Huang, Pengzhou AU - Huang P AD - National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China. LA - eng PT - Journal Article DEP - 20230613 PL - England TA - Connect Tissue Res JT - Connective tissue research JID - 0365263 RN - 0 (RNA, Long Noncoding) RN - 0 (MicroRNAs) RN - EC 3.1.26.3 (DICER1 protein, human) RN - EC 3.1.26.3 (Ribonuclease III) RN - EC 3.6.4.13 (DEAD-box RNA Helicases) RN - 0 (CDC5L protein, human) SB - IM MH - Humans MH - *RNA, Long Noncoding/genetics/metabolism MH - In Situ Hybridization, Fluorescence MH - Cell Proliferation/genetics MH - Cell Cycle/genetics MH - *Osteosarcoma/genetics MH - *Bone Neoplasms/genetics/metabolism/pathology MH - Apoptosis/genetics MH - Cell Line, Tumor MH - Cell Movement/genetics MH - *MicroRNAs/genetics MH - Gene Expression Regulation, Neoplastic MH - Ribonuclease III/genetics/metabolism MH - DEAD-box RNA Helicases/genetics/metabolism OTO - NOTNLM OT - CDC5L OT - DICER1-AS1 OT - Osteosarcoma OT - cell cycle OT - nuclear/cytosolic sublocation EDAT- 2023/06/13 13:12 MHDA- 2023/10/27 06:42 CRDT- 2023/06/13 08:33 PHST- 2023/10/27 06:42 [medline] PHST- 2023/06/13 13:12 [pubmed] PHST- 2023/06/13 08:33 [entrez] AID - 10.1080/03008207.2023.2223289 [doi] PST - ppublish SO - Connect Tissue Res. 2023 Nov;64(6):519-531. doi: 10.1080/03008207.2023.2223289. Epub 2023 Jun 13.