circPVT1 promotes osteosarcoma glycolysis and metastasis by sponging miR-423-5p to activate Wnt5a/Ror2 signaling.

Osteosarcoma (OS) is the most prevalent form of bone cancer. It has a high metastatic potential and progresses rapidly. The molecular mechanisms of OS remain unclear and this study aims to examine the functional role of circPVT1 and miR-423-5p in OS. Quantitative RT-PCR (qRT-PCR) and western blotting were used to examine levels of miR-423-5p, circPVT1, Wnt5a, Ror2, and glycolysis-related proteins, including HK2, PKM2, GLUT1, and LDHA. Colony formation and transwell assays were used to test the roles of miR-423-5p, circPVT1, and Wnt5a/Ror2 in OS cell proliferation, migration, and invasion. Dual luciferase assay and Ago2-RIP were used to validate the interactions of miR-423-5p/Wnt5a, miR-423-5p/Ror2, and circPVT1/miR-423-5p. Glucose uptake assay and measurement of lactate production were performed to assess the glycolysis process. A nude mouse xenograft model was used to evaluate the effects of sh-circPVT1 and miR-423-5p mimics on tumor growth and metastasis in vivo. miR-423-5p was reduced in both OS tissues and OS cell lines, while Wnt5a/Ror2 and circPVT1 were elevated. miR-423-5p bound to 3'-UTR of Wnt5a and Ror2 mRNA, and inhibited glycolysis and OS cell proliferation, migration, and invasion by targeting Wnt5a and Ror2. circPVT1 interacted with miR-423-5p and activated Wnt5a/Ror2 signaling by sponging miR-423-5p. Knockdown of circPVT1 or overexpression of miR-423-5p suppressed OS tumor growth and metastasis in vivo. miR-423-5p inhibited OS glycolysis, proliferation, migration, and metastasis by targeting and suppressing Wnt5a/Ror2 signaling pathway, while circPVT1 promoted those processes by acting as a sponge of miR-423-5p.

Wan J ，Liu Y ，Long F ，Tian J ，Zhang C ... -  《-》

circPVT1 regulates medullary thyroid cancer growth and metastasis by targeting miR-455-5p to activate CXCL12/CXCR4 signaling.

Zheng X ，Rui S ，Wang XF ，Zou XH ，Gong YP ，Li ZH ... -  《-》

MicroRNA-124 suppresses the migration and invasion of osteosarcoma cells via targeting ROR2-mediated non-canonical Wnt signaling.

Zhang C ，Hu Y ，Wan J ，He H ... -  《-》

Downregulation of long non-coding RNA UCA1 represses tumorigenesis and metastasis of osteosarcoma via miR-513b-5p/E2F5 axis.

Long non-coding RNAs have the regulatory roles in different kinds of human cancers. The key point of this study was to research the functional mechanisms of urothelial carcinoma associated 1 (UCA1) in the development of osteosarcoma. Quantitative real-time PCR was adopted for the expression detection of UCA1, microRNA-513b-5p (miR-513b-5p) and E2F transcription factor 5 (E2F5). The target relation was verified via dual-luciferase reporter assay and RNA pull-down assay. Cell proliferation was evaluated using Cell Counting Kit-8 and colony formation assays. Transwell assay was applied to assess cell migration and invasion. Western blot was performed for protein examination. Xenograft experiment was used to explore the effect of UCA1 on osteosarcoma in vivo. UCA1 expression was enhanced while miR-513b-5p was refrained in osteosarcoma tissues and cells. MiR-513b-5p was a target of UCA1. Inhibition of UCA1 or overexpression of miR-513b-5p suppressed osteosarcoma cell proliferation, migration and invasion. E2F5 was identified as a downstream gene of miR-513b-5p. MiR-513b-5p inhibitor or E2F5 overexpression rescued the progression inhibition of osteosarcoma by UCA1 knockdown, and UCA1 regulated E2F5 and Cyclin E expression by targeting miR-513b-5p. Downregulation of UCA1 restrained the tumorigenesis of osteosarcoma in vivo through the miR-513b-5p/E2F5 axis. Collectively, knockdown of UCA1 inhibited tumorigenesis and metastasis of osteosarcoma via regulating the miR-513b-5p/E2F5 axis. UCA1 might be a biological indicator in the progression and treatment of osteosarcoma.

Zhang Z ，Wu X ，Han Q ，Huang Z ... -  《-》

miR-485-3p regulated by MALAT1 inhibits osteosarcoma glycolysis and metastasis by directly suppressing c-MET and AKT3/mTOR signalling.

Osteosarcoma (OS) is an extremely malignant bone cancer with high incidence and rapid progression. This study aims to investigate the role and underlying mechanisms of MALAT1 and miR-485-3p in OS. qRT-PCR and Western blotting were utilized to measure the levels of miR-485-3p, MALAT1, c-MET, AKT3, p-mTOR, mTOR, glycolysis-related proteins or migration-related proteins. Colony formation and transwell assay were used to test the roles of miR-485-3p, MALAT1, c-MET and AKT3 in cancer cell proliferation, migration and invasion. Dual luciferase assay was used to validate the interactions of miR-485-3p/c-MET, miR-485-3p/AKT3, and MALAT1/miR-485-3p. Glucose uptake assay and measurement of lactate production were employed to determine the glycolysis process. Mouse tumour xenograft model was used to determine the effect of shMALAT1 and miR-485-3p mimics on tumour growth and metastasis in vivo. miR-485-3p was decreased while c-MET, AKT3, and MALAT1 were increased in human OS tissues and cells. miR-485-3p bound directly to c-MET and AKT3 mRNAs and repressed OS cell glycolysis, proliferation, migration, and invasion through decreasing glycolysis-related proteins and migration-related proteins via inhibiting c-MET and AKT3/mTOR pathway. In addition, MALAT1 interacted with miR-485-3p and disinhibited c-MET and AKT3/mTOR signalling. Knockdown MALAT1 or overexpression of miR-485-3p restrained OS tumour growth and lung metastasis in vivo. miR-485-3p suppresses OS glycolysis, proliferation, and metastasis via inhibiting c-MET and AKT3/mTOR signalling and MALAT1 acts as a sponge of miR-485-3p. MALAT1 and miR-485-3p may be the key regulators in OS progression, and potential molecular targets for future OS therapy.

Wang Q ，Liu MJ ，Bu J ，Deng JL ，Jiang BY ，Jiang LD ，He XJ ... -  《-》