PMID- 34512027 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220426 IS - 1179-1322 (Print) IS - 1179-1322 (Electronic) IS - 1179-1322 (Linking) VI - 13 DP - 2021 TI - MALAT-1 is Associated with the Doxorubicin Resistance in U-2OS Osteosarcoma Cells. PG - 6879-6889 LID - 10.2147/CMAR.S304922 [doi] AB - PURPOSE: Our study aimed to investigate the relationship between MALAT-1 (metastasis-associated lung adenocarcinoma transcript 1) expression and the chemotherapy drug resistance in osteosarcoma. METHODS: The U-2OS osteosarcoma cell line was selected for the experiment. The cells were treated with methotrexate, doxorubicin, cisplatin, and ifosfamide, respectively. RT-PCR was applied to detect the MALAT-1 expression in cells. The doxorubicin-resistant cell line was constructed. The cells were divided into doxorubicin-sensitivity group (DS/shCtrl), doxorubicin-resistance group (DR/shCtrl) and shMALAT1-doxorubicin-resistance group (DR/shMALAT1). The colony formation assay and 5-ethynyl-2'-deoxyuridine (EdU) assay were used to detect cell proliferation. PI staining was used to detect the cell cycle. Transwell assay and wound healing assay were used to observe the migration and invasion ability. Annexin V-FITC assay was used to detect cell apoptosis. Western blot was used to detect the protein expression and potential mechanism. The impacts of MALAT-1 expression were verified in vivo. RESULTS: The MALAT-1 was upregulated in the doxorubicin-resistant U-2OS osteosarcoma cells. Downregulating MALAT-1 in the doxorubicin-resistant cells inhibited the proliferation, migration, and invasiveness, increased the ratio of cells in the G0/G1 phase, promoted apoptosis. In the doxorubicin-resistant U-2OS cells, the extracellular regulated protein kinases (ERK) phosphorylation was declined, which could be reversed by downregulating MALAT-1. In vivo assay indicated that the growth of doxorubicin-resistant solid osteosarcoma could be suppressed by downregulating MALAT-1. CONCLUSION: Our study provides evidence that doxorubicin may upregulate MALAT-1 in osteosarcoma. Downregulating MALAT-1 in the doxorubicin resistance U-2OS cells could reverse the resistance and may improve chemotherapeutic efficiency. Some conclusions in previous literature may be one-sided. CI - (c) 2021 Liu et al. FAU - Liu, Chang AU - Liu C AD - Department of Orthopedics, The 900th Hospital of Joint Logistic Support Force, Fuzhou, Fujian Province, 350025, People's Republic of China. AD - Department of Orthopedics, Changhai Hospital Affiliated to the Naval Medical University, Shanghai, 200433, People's Republic of China. FAU - Han, Xuesong AU - Han X AD - Department of Orthopedics, The 900th Hospital of Joint Logistic Support Force, Fuzhou, Fujian Province, 350025, People's Republic of China. FAU - Li, Bo AU - Li B AD - Department of Orthopedics, Changhai Hospital Affiliated to the Naval Medical University, Shanghai, 200433, People's Republic of China. FAU - Huang, Shaobin AU - Huang S AD - Department of Orthopedics, The 900th Hospital of Joint Logistic Support Force, Fuzhou, Fujian Province, 350025, People's Republic of China. FAU - Zhou, Zhong AU - Zhou Z AD - Department of Orthopedics, The 900th Hospital of Joint Logistic Support Force, Fuzhou, Fujian Province, 350025, People's Republic of China. FAU - Wang, Zhiwei AU - Wang Z AD - Department of Orthopedics, Changhai Hospital Affiliated to the Naval Medical University, Shanghai, 200433, People's Republic of China. FAU - Wang, Wanming AU - Wang W AD - Department of Orthopedics, The 900th Hospital of Joint Logistic Support Force, Fuzhou, Fujian Province, 350025, People's Republic of China. LA - eng PT - Journal Article DEP - 20210901 PL - New Zealand TA - Cancer Manag Res JT - Cancer management and research JID - 101512700 PMC - PMC8421671 OTO - NOTNLM OT - MALAT-1 OT - chemotherapy resistance OT - doxorubicin OT - extracellular regulated protein kinases OT - long noncoding RNA OT - osteosarcoma COIS- The authors report no conflicts of interest in this work. EDAT- 2021/09/14 06:00 MHDA- 2021/09/14 06:01 PMCR- 2021/09/01 CRDT- 2021/09/13 06:38 PHST- 2021/02/02 00:00 [received] PHST- 2021/08/18 00:00 [accepted] PHST- 2021/09/13 06:38 [entrez] PHST- 2021/09/14 06:00 [pubmed] PHST- 2021/09/14 06:01 [medline] PHST- 2021/09/01 00:00 [pmc-release] AID - 304922 [pii] AID - 10.2147/CMAR.S304922 [doi] PST - epublish SO - Cancer Manag Res. 2021 Sep 1;13:6879-6889. doi: 10.2147/CMAR.S304922. eCollection 2021.