OncoTargets and Therapy (Sep 2020)
Long Noncoding RNA LINC00525 Promotes the Aggressive Phenotype of Chordoma Through Acting as a microRNA-505-3p Sponge and Consequently Raising HMGB1 Expression
Abstract
Lei Li, Guohua Lv, Bing Wang, Hong Ma Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of ChinaCorrespondence: Hong MaDepartment of Spine Surgery, The Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha, Hunan 410011, People’s Republic of ChinaEmail [email protected]: Long intergenic non-protein coding RNA 525 (LINC00525), a long noncoding RNA, has been implicated in the carcinogenesis and progression of many human cancer types. However, the detailed roles of LINC00525 in chordoma and the underlying mechanisms are not fully understood. Here, we aimed to determine whether LINC00525 could modulate the oncogenicity of chordoma cells and to elucidate in detail the molecular events underlying these tumor-promoting activities.Methods: Reverse-transcription quantitative polymerase chain reactions were performed to assess LINC00525 expression in chordoma. The effects of LINC00525 silencing on chordoma cell proliferation, apoptosis, migration, and invasiveness in vitro and tumor growth in vivo were respectively tested using CCK-8 assay, flow cytometry, migration and invasion assays, and xenograft experiments.Results: High LINC00525 expression levels were detected in chordoma tissues. The proliferative, migratory, and invasive abilities of chordoma cells in vitro and their tumor growth in vivo were suppressed by the LINC00525 knockdown, whereas apoptosis was induced by it. Mechanistically, LINC00525 acted as a molecular sponge of microRNA-505-3p (miR-505-3p) and upregulated the expression of high mobility group box 1 (HMGB1), which is directly targeted by miR-505-3p. Rescue assays indicated that increasing the output of miR-505-3p–HMGB1 axis attenuated the effects of LINC00525 depletion on chordoma cells.Conclusion: LINC00525, a pro-oncogenic long noncoding RNA, promotes chordoma progression by regulating the miR-505-3p–HMGB1 axis. The LINC00525–miR-505-3p–HMGB1 pathway may be a novel therapeutic target in chordoma.Keywords: chordoma, LINC00525, miR-505-3p, HMGB1, oncogenicity
