Mechanisms underlying the promotion of osteosarcoma cell proliferation and invasion by lncRNA PBB12.

PBB12, a long noncoding RNA (lncRNA), has not been reported to be involved in the progression of osteosarcoma to date. According to our research data, it was found that osteosarcoma patients with a high PBB12 level frequently showed increased metastasis. Mechanistic research demonstrated that PBB12 can competitively bind to hsa-miR-204-5p by acting as a microRNA sponge. Furthermore, PBB12 intervenes in the Kruppel-like factor 4 (KLF4)/hsa-miR-204-5p/activating transcription factor 2 (ATF2) pathway and affects the proliferation and invasion of osteosarcoma cells. High PBB12 expression was founld to lead to the loss of function of the cancer suppressors KLF4 and hsa-miR-204-5p; these effects are the intrinsic reason why osteosarcoma patients with high levels of PBB12 often develop tumor metastases. In vitro functional experimental data showed that in the osteosarcoma cell lines MG63 and SAOS-2, PBB12 silencing and overexpression significantly increases or reversed the inhibitory effect of KLF4 on the proliferation and invasion of tumor cells, respectively. The involvement of the interaction between PBB12 and the KLF4/hsa-miR-204-5p/ATF2 pathway in osteosarcoma progression was reported for the first time, and these data provide important theoretical support for gene therapy targeting KLF4 and hsa-miR-204-5p. The great significance of this study is that a high or low genetic background level of PBB12 in osteosarcoma patients may serve as an important marker for screening patients for a high risk of tumor metastasis. Furthermore, for osteosarcoma patients with high PBB12 expression, the primary task for all accurate personalized clinical treatment programs may be the determination of how to effectively knock down PBB12 in tumor bodies.