LINC00657 activates PD-L1 to promote osteosarcoma metastasis via miR-106a.

Osteosarcoma (OS) cells are one of the primary cancer-related causes of death around the world. Long noncoding RNAs are key for OS progression; however, the detailed molecular mechanism remains unknown. LINC00657, miR-106a, and programmed death ligand-1 (PD-L1) genes expression were detected by reverse transcription-quantitative PCR (RT-qPCR) and Western blot approaches. Invasion and lymphangiogenesis were studied using transwell invasion assay and lymphatic vessel formation assay, respectively. We used bioinformatic analyses to identify putative targets of LINC00657 and miR-106a. Luciferase activity was measured by dual-luciferase reporter assay. PD-L1 protein levels were examined by flow cytometry experiments. LINC00657 knockdown attenuates cell invasion and tumor growth of MG63 and lymphatic vessel formation. miR-106a directly binds LINC00657 and they regulate each other. Furthermore, miR-106a inhibitor strikingly enhanced lymphatic vessel formation and invasion of shLINC00657 MG63 cells. miR-106a mimic directly targeted and downregulated PD-L1. PD-L1 overexpression largely rescued miR-106a mimic-modulated OS cell metastasis. LINC00657 and PD-L1 were upregulated in clinical OS tumors compared to normal tissues. Lower expression levels of LINC00657 and PD-L1 were closely associated with higher overall survival of patients with OS. Here, we suggest a novel mechanism for LINC00657-regulated metastasis of OS cells by regulating the miR-106a/PD-L1 axis. Our conclusions facilitate the development of therapeutical approaches by targeting LINC00657.