Qibo Zhang1, Huachang Jiang2, Youming Jin3, Ning Zhang4, Zhihua Mu4, Yan Guo5, Haitao Li6. 1. Department of Ultrasound, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University Weihai 264200, Shandong Province, China. 2. Trauma Surgery Department, Dongying District People's Hospital Dongying 257100, Shandong Province, China. 3. Department of Orthopaedics, Gaoqing People's Hospital Zibo 256300, Shandong Province, China. 4. Department of Orthopaedics, Zhaoyuan People's Hospital Yantai 265400, Shandong Province, China. 5. Palliative Medicine Center, Xinkun Hua Hospital, The First People's Hospital of Yunnan Province Kunming 650100, Yunnan Province, China. 6. Department of Joint Surgery, Linyi People's Hospital Linyi 276000, Shandong Province, China.
Abstract
OBJECTIVE: Osteosarcoma (OS) is a common bone cancer that usually influences children. Metastasis and recurrence are the main reasons for the poor prognosis. In this study, we investigated the functions and mechanisms of KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) in OS. METHODS: Cell viability and proliferation were detected using the CCK-8 assay and the 5-Ethynyl-2'-deoxyuridine (EdU) assay. Wound-healing assays, transwell assay and flow cytometry were used to identify cell migration, invasion, and apoptosis, respectively. The relationship among KCNQ1OT1, miR-154-3p, and KLF12 was verified by luciferase reporter assay and restricting protein immunoprecipitation (RIP) assay. Xenograft models were established to confirm the function of KCNQ1OT1 in vivo. RESULTS: The expression of KCNQ1OT1 was higher in OS than in non-tumor tissues and cells. Knockdown of KCNQ1OT1 could reduce OS cell proliferation, migration, and invasion and promoted cell death. Mechanistically, KCNQ1OT1 contributed to OS formation by acting as a competitive endogenous RNA (ceRNA) and influencing miR-154-3p expression. Furthermore, we confirmed that miR-154-3p affected KLF12 expression through binding the 3'UTR region. Finally, rescue experiments determined that KCNQ1OT1 exerted major roles in OS through the miR-154-3p/KLF12 axis. CONCLUSION: In conclusion, our research explains the mechanism of KCNQ1OT1 in OS progression, which could serve as a new therapeutic target. AJTR
OBJECTIVE: Osteosarcoma (OS) is a common bone cancer that usually influences children. Metastasis and recurrence are the main reasons for the poor prognosis. In this study, we investigated the functions and mechanisms of KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) in OS. METHODS: Cell viability and proliferation were detected using the CCK-8 assay and the 5-Ethynyl-2'-deoxyuridine (EdU) assay. Wound-healing assays, transwell assay and flow cytometry were used to identify cell migration, invasion, and apoptosis, respectively. The relationship among KCNQ1OT1, miR-154-3p, and KLF12 was verified by luciferase reporter assay and restricting protein immunoprecipitation (RIP) assay. Xenograft models were established to confirm the function of KCNQ1OT1 in vivo. RESULTS: The expression of KCNQ1OT1 was higher in OS than in non-tumor tissues and cells. Knockdown of KCNQ1OT1 could reduce OS cell proliferation, migration, and invasion and promoted cell death. Mechanistically, KCNQ1OT1 contributed to OS formation by acting as a competitive endogenous RNA (ceRNA) and influencing miR-154-3p expression. Furthermore, we confirmed that miR-154-3p affected KLF12 expression through binding the 3'UTR region. Finally, rescue experiments determined that KCNQ1OT1 exerted major roles in OS through the miR-154-3p/KLF12 axis. CONCLUSION: In conclusion, our research explains the mechanism of KCNQ1OT1 in OS progression, which could serve as a new therapeutic target. AJTR