Dataset Information

Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts.

ABSTRACT: Bone is a frequent metastatic site of non-small cell lung cancer (NSCLC), and bone metastasis (BoM) presents significant challenges for patient survival and quality of life. Osteolytic BoM is characterised by aberrant differentiation and malfunction of osteoclasts through modulation of the TGF-β/pTHrP/RANKL signalling pathway, but its upstream regulatory mechanism is unclear. In this study, we found that lncRNA-SOX2OT was highly accumulated in exosomes derived from the peripheral blood of NSCLC patients with BoM and that patients with higher expression of exosomal lncRNA-SOX2OT had significantly shorter overall survival. Additionally, exosomal lncRNA-SOX2OT derived from NSCLC cells promoted cell invasion and migration in vitro, as well as BoM in vivo. Mechanistically, we discovered that NSCLC cell-derived exosomal lncRNA-SOX2OT modulated osteoclast differentiation and stimulated BoM by targeting the miRNA-194-5p/RAC1 signalling axis and TGF-β/pTHrP/RANKL signalling pathway in osteoclasts. In conclusion, exosomal lncRNA-SOX2OT plays a crucial role in promoting BoM and may serve as a promising prognostic biomarker and treatment target in metastatic NSCLC.

SUBMITTER: Ni J

PROVIDER: S-EPMC8253828 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts.

Ni Jianjiao J Zhang Xiaofei X Li Juan J Zheng Zhiqin Z Zhang Junhua J Zhao Weixin W Liu Liang L

Cell death & disease 20210702 7

Bone is a frequent metastatic site of non-small cell lung cancer (NSCLC), and bone metastasis (BoM) presents significant challenges for patient survival and quality of life. Osteolytic BoM is characterised by aberrant differentiation and malfunction of osteoclasts through modulation of the TGF-β/pTHrP/RANKL signalling pathway, but its upstream regulatory mechanism is unclear. In this study, we found that lncRNA-SOX2OT was highly accumulated in exosomes derived from the peripheral blood of NSCLC ...[more]

PMID: 34215717

Similar Datasets

Project description:BackgroundHepatocellular carcinoma (HCC) is the most common malignant liver tumor with poor clinical outcomes. Increasing amount of long non-coding RNAs (lncRNAs) have been revealed to be implicated in the carcinogenesis and progression of HCC. However, the expressions, clinical significances, and roles of most lncRNAs in HCC are still unknown.MethodsThe expression of lncRNA MCM3AP antisense RNA 1 (MCM3AP-AS1) in HCC tissues and cell lines was detected by qRT-PCR and fluorescence in situ hybridization. Immunoblotting, CCK-8, EdU, colony formation and flow cytometry were performed to investigate the role of MCM3AP-AS1 in HCC cell proliferation, cell cycle and apoptosis in vitro. A subcutaneous tumor mouse model was constructed to analyze in vivo growth of HCC cells after MCM3AP-AS1 knockdown. The interactions among MCM3AP-AS1, miR-194-5p and FOXA1 were measured by RNA pull-down, RNA immunoprecipitation and luciferase reporter assay.ResultsWe revealed a novel oncogenic lncRNA MCM3AP-AS1, which is overexpressed in HCC and positively correlated with large tumor size, high tumor grade, advanced tumor stage and poor prognosis of HCC patients. MCM3AP-AS1 knockdown suppressed HCC cell proliferation, colony formation and cell cycle progression, and induced apoptosis in vitro, and depletion of MCM3AP-AS1 inhibited tumor growth of HCC in vivo. Mechanistically, MCM3AP-AS1 directly bound to miR-194-5p and acted as competing endogenous RNA (ceRNA), and subsequently facilitated miR-194-5p's target gene forkhead box A1 (FOXA1) expression in HCC cells. Interestingly, FOXA1 restoration rescued MCM3AP-AS1 knockdown induced proliferation inhibition, G1 arrest and apoptosis of HCC cells.ConclusionsOur results recognized MCM3AP-AS1 as a novel oncogenic lncRNA, which indicated poor clinical outcomes in patients with HCC. MCM3AP-AS1 exerted an oncogenic role in HCC via targeting miR-194-5p and subsequently promoted FOXA1 expression. Our findings suggested that MCM3AP-AS1 could be a potential prognostic biomarker and therapeutic target for HCC.

Project description:BackgroundNumerous studies proved that long non-coding RNA (lncRNA) is involved in the progression of multifarious diseases, especially in some carcinomas. As a potential tumor biomarker, plasmacytoma variant translocation 1 gene (PVT1) is involved in the development and progression of multifarious cancers. Nevertheless, the intrinsic and concrete molecular mechanism of PVT1 in bladder cancer still remained unclear, which is also the dilemma faced in many non-coding RNA studies.ResultsOur research revealed that PVT1 was significantly higher expression in bladder carcinoma specimens and cell lines. Further experiments indicated that knockdown or overexpression of PVT1 restrained or promoted the malignant phenotype and WNT/β-catenin signaling in bladder cancer cells. Meanwhile miR-194-5p was in contrast and miR-194-5p could partially reverse the function of PVT1 in malignant bladder tumor cells. As a microRNA sponge, PVT1 actively promotes the expression of b-cells lymphoma-2-associated transcription factor 1 (BCLAF1) to sponge miR-194-5p and subsequently increases malignant phenotypes of bladder cancer cells. Therefore, it performs a carcinogenic effect and miR-194-5p as the opposite function, and serves as an antioncogene in the bladder carcinomas pathogenesis.ConclusionPVT1-miR-194-5p-BCLAF1 axis is involved in the malignant progression and development of bladder carcinomas. Experiments revealed that PVT1 has a significant regulatory effect on bladder cancer (BC) and can be used as a clinical diagnostic marker and a therapeutic molecular marker for patients suffering from BC.MethodsIn urothelial bladder carcinoma specimens and cell lines, the relative expression levels of PVT1 and miR-194-5p were detected by quantitative reverse transcription PCR (RT-qPCR). Through experiments such as loss-function and over-expression, the biological effects of PVT1 and miR-194-5p on the proliferation, migration, apoptosis and tumorigenicity were explored in bladder cancer cells. Co-immunoprecipitation, proteomics experiments, dual luciferase reporter gene analysis, western blot and other methods were adopted to investigate the PVT1 potential mechanism in bladder carcinomas.

Dataset Information

Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts.

Publications

Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets