LncRNA KCNQ1OT1 acting as a ceRNA for miR-4458 enhances osteosarcoma progression by regulating CCND2 expression
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Osteosarcoma is prevalent worldwide and characterized as a challenging health burden. It has been increasingly indicated that long non-coding RNAs (lncRNAs) are significant in pathological processes of numerous cancers, exerting oncogenic or tumor-suppressive function. However, the participation of KCNQ1OT1 in osteosarcoma has not been elaborated. In this study, we focus on interrogating the function of KCNQ1OT1 and its underlying mechanism in osteosarcoma. Our work demonstrated the upregulation of KCNQ1OT1 in osteosarcoma through qRT-PCR. Besides, loss of function assay (CCK-8, transwell migration) indicated KCNQ1OT1 promoted cell proliferation, migration in osteosarcoma. Mechanically, KCNQ1OT1 acting as sponge for miR-4458 antagonized its tumor-suppressive impact on CCND2 expression. The anti-apoptotic nature of KCNQ1OT1 was also unveiled via caspase-3 activity assay. Overexpressed KCNQ1OT1 acted as competing endogenous RNA (ceRNA) for miR-4458 and subsequently reinforced target gene CCND2. Collectively, the results of rescue experiments suggested that the oncogenic role of KCNQ1OT1 was performed through sponging miR-4458 and upregulating CCND2 during osteosarcoma development, providing a novel perspective of intervention in osteosarcoma management.
KeywordsKCNQ1OT1 miR-4458 CCND2 Osteosarcoma
We are thankful to all who participated in this study.
Compliance with ethical standards
The Research Ethics Committee of this hospital gave consent to this study. Prior to diagnosis, none of patients were subjected to antitumor treatment. The written consents were eligibly gained from OS patients and in line with the Declaration of Helsinki, the study was implemented.
Conflict of interest
The authors declare that they have no conflict of interest.
- Silva JM, Rodrigues S, Sampaio-Marques B, Gomes P, Neves-Carvalho A, Dioli C, Soares-Cunha C, Mazuik BF, Takashima A, Ludovico P, Wolozin B, Sousa N, Sotiropoulos I (2018) Dysregulation of autophagy and stress granule-related proteins in stress-driven Tau pathology. Cell Death Differ. https://doi.org/10.1038/s41418-018-0217-1
- Su X, Teng J, Jin G, Li J, Zhao Z, Cao X, Guo Y, Guo M, Li X, Wu J, Wang C, Guo Z, Guo Q (2019) ELK1-induced upregulation of long non-coding RNA MIR100HG predicts poor prognosis and promotes the progression of osteosarcoma by epigenetically silencing LATS1 and LATS2. Biomed Pharmacother 109:788–797CrossRefGoogle Scholar
- Wagner F, Holzapfel BM, McGovern JA, Shafiee A, Baldwin JG, Martine LC, Lahr CA, Wunner FM, Friis T, Bas O, Boxberg M, Prodinger PM, Shokoohmand A, Moi D, Mazzieri R, Loessner D, Hutmacher DW (2018) Humanization of bone and bone marrow in an orthotopic site reveals new potential therapeutic targets in osteosarcoma. Biomaterials 171:230–246CrossRefGoogle Scholar
- Wang D, Niu X, Wang Z, Song CL, Huang Z, Chen KN, Duan J, Bai H, Xu J, Zhao J, Wang Y, Zhuo M, Xie XS, Kang X, Tian Y, Cai L, Han JF, An T, Sun Y, Gao S, Zhao J, Ying J, Wang L, He J, Wang J (2019) Multiregion sequencing reveals the genetic heterogeneity and evolutionary history of osteosarcoma and matched pulmonary metastases. Cancer Res 79:7–20CrossRefGoogle Scholar
- Wang Z, Wu H, Xue M, Lin P, Wang S, Lin N, Huang X, Pan W, Liu M, Yan X, Qu H, Sun L, Li H, Wu Y, Teng W, Wang Z, Zhou X, Chen H, Poznansky MC, Ye Z (2018b) Epigenetic regulation of CXCL12 plays a critical role in mediating tumor progression and the immune response in osteosarcoma. Cancer Res 78:3938–3953CrossRefGoogle Scholar
- Xie Y, Sundström A, Maturi NP, Tan EJ, Marinescu VD, Jarvius M, Tirfing M, Jin C, Chen L, Essand M, Swartling FJ, Nelander S, Jiang Y, Uhrbom L (2018) LGR5 promotes tumorigenicity and invasion of glioblastoma stem-like cells and is a potential therapeutic target for a subset of glioblastoma patients. J Pathol 247:228–240. https://doi.org/10.1002/path.5186 CrossRefGoogle Scholar
- Yu HM, Wang C, Yuan Z, Chen GL, Ye T, Yang BW (2018) LncRNA NEAT1 promotes the tumorigenesis of colorectal cancer by sponging miR-193a-3p. Cell Prolif. https://doi.org/10.1111/cpr.12526:e12526