LncRNA LINC00313 Knockdown Inhibits Tumorigenesis and Metastasis in Human Osteosarcoma by Upregulating FOSL2 through Sponging miR-342-3p

Chen, Hongtao; Wahafu, Paerhati; Wang, Leilei; Chen, Xuan

doi:10.3349/ymj.2020.61.5.359

Cited by 17 publications

(9 citation statements)

References 28 publications

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“…In the present study, we performed data mining using public databases to show that LINC00313 expression was upregulated significantly in TGCT tissue and that there was significantly association between DFI survival and LINC00313 expression. This is similar to the findings of another research team in osteosarcoma [ 27 ] and cervical carcinoma [ 28 ], who found that patients with high LINC00313 expression had poorer overall and disease-free survival. Moreover, the expression of LINC00313 has a good diagnostic value for TGCT.…”

Section: Discussionsupporting

confidence: 90%

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LINC00313 regulates the metastasis of testicular germ cell tumors through epithelial-mesenchyme transition and immune pathways

et al. 2022

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Testicular germ cell tumor (TGCT) is a relatively rare entity tumor, accounting for only 1% of all male cancers. However, it is the most common solid tumor in young men between 15 and 34 years old. Long noncoding RNAs (lncRNAs) are involved in various physiological and pathological processes. However, the functions of lncRNAs in TGCT have only rarely been investigated. LncRNAs associated with TGCT were identified using Gene Expression Omnibus (GEO) database and UCSC XENA database data mining. The effects of LINC00313 on NCCIT cell migration and invasion were evaluated in transwell assays. The expression levels of epithelial-mesenchyme transition (EMT)-related proteins in cells knockdown of LINC00313 were analyzed by Western blot. Correlation analyses between lncRNA LINC00313 expression and copy number variation (CNV) and immune cell infiltration were carried out using The Cancer Genome Atl as (TCGA) data. The effect of Panobinostatin targeting LINC00313 in TGCT cells was investigated. We observed higher LINC00313 expression in TGCT. The migratory and invasive properties of TGCT cells were augmented by LINC00313 , likely via its effects on modulating the expression of epithelial-mesenchyme transition (EMT) related proteins: CTNNB1, ZEB1, CDH2, Snail and VIM. Moreover, LINC00313 expression and CNV correlated negatively with the infiltration of immune cells. In addition, Panobinostat might be a possible candidate drug to target LINC00313 in TGCT. LINC00313 performs important pro-migration and invasion functions in the pathogenesis of TGCT. LINC00313 could be used as diagnostic, prognostic, immune marker and therapeutic target to develop effective treatment of TGCT.

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Section: Discussionsupporting

confidence: 90%

“…For example, LINC00313 was reported to be highly expressed in lung cancer and to indicate shorter overall survival (OS) [ 26 ]. High expression of LINC00313 was associated with shorter OS in osteosarcoma [ 27 ]. To the best of our knowledge, the expression and role of LINC00313 in TGCT has not been reported.…”

Section: Discussionmentioning

confidence: 99%

LINC00313 regulates the metastasis of testicular germ cell tumors through epithelial-mesenchyme transition and immune pathways

et al. 2022

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“…Similarly, the lncRNA Sox2OT-V7 regulates ULK1, ATG4A, and ATG5 through miR-142/miR-22 to modulate autophagy in osteosarcoma cells (Zhu et al, 2020). The lncRNA LINC00313 acts as a sponge for miR-342-3p, regulating FOSL2 levels and inhibiting autophagy in human osteosarcoma cells, ultimately suppressing osteosarcoma cell metastasis (Chen et al, 2020). LncRNA-ATB modulates autophagy in liver cancer cells by activating Yes-associated protein (YAP) and inducing ATG5 expression, associated with poor prognosis of liver cancer patients (Wang C.Z.…”

Section: Introductionmentioning

confidence: 99%

Development of a Machine Learning-Based Autophagy-Related lncRNA Signature to Improve Prognosis Prediction in Osteosarcoma Patients

Zhang

et al. 2021

Front. Mol. Biosci.

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BackgroundOsteosarcoma is a frequent bone malignancy in children and young adults. Despite the availability of some prognostic biomarkers, most of them fail to accurately predict prognosis in osteosarcoma patients. In this study, we used bioinformatics tools and machine learning algorithms to establish an autophagy-related long non-coding RNA (lncRNA) signature to predict the prognosis of osteosarcoma patients.MethodsWe obtained expression and clinical data from osteosarcoma patients in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. We acquired an autophagy gene list from the Human Autophagy Database (HADb) and identified autophagy-related lncRNAs by co-expression analyses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the autophagy-related lncRNAs were conducted. Univariate and multivariate Cox regression analyses were performed to assess the prognostic value of the autophagy-related lncRNA signature and validate the relationship between the signature and osteosarcoma patient survival in an independent cohort. We also investigated the relationship between the signature and immune cell infiltration.ResultsWe initially identified 69 autophagy-related lncRNAs, 13 of which were significant predictors of overall survival in osteosarcoma patients. Kaplan-Meier analyses revealed that the 13 autophagy-related lncRNAs could stratify patients based on their outcomes. Receiver operating characteristic curve analyses confirmed the superior prognostic value of the lncRNA signature compared to clinically used prognostic biomarkers. Importantly, the autophagy-related lncRNA signature predicted patient prognosis independently of clinicopathological characteristics. Furthermore, we found that the expression levels of the autophagy-related lncRNA signature were significantly associated with the infiltration levels of different immune cell subsets, including T cells, NK cells, and dendritic cells.ConclusionThe autophagy-related lncRNA signature established here is an independent and robust predictor of osteosarcoma patient survival. Our findings also suggest that the expression of these 13 autophagy-related lncRNAs may promote osteosarcoma progression by regulating immune cell infiltration in the tumor microenvironment.

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“…MiR-342-3p could repress colorectal cancer chemoresistance [ 25 ], and could act synergistically with miR-205-5p to reduce tumor chemoresistance by inhibiting E2F1 [ 26 ]. MiR-342-3p had an obvious tendency of low expression in OS, and has been proved to inhibit the progression and promote the radiosensitivity of OS [ 27 – 29 ]. Our study discovered that miR-342-3p was underexpressed in the DXR-resistant OS tissues and cells, and it also hindered OS DXR resistance.…”

Section: Discussionmentioning

confidence: 99%

Hsa_circ_0004674 promotes osteosarcoma doxorubicin resistance by regulating the miR-342-3p/FBN1 axis

Yumei

Bai

et al. 2021

J Orthop Surg Res

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Background The occurrence of chemoresistance is a common problem in tumor treatment. Circular RNA (circRNA) has been confirmed to be related to tumor chemoresistance. However, the role and the underlying molecular mechanism of hsa_circ_0004674 in the chemoresistance of osteosarcoma (OS) are still unclear. Methods The expression of hsa_circ_0004674, miR-342-3p, and fibrillin-1 (FBN1) was determined by qRT-PCR. Cell counting kit 8 assay was used to evaluate the doxorubicin (DXR) resistance of cells. The proliferation and apoptosis of cells were measured using colony formation assay and flow cytometry. Western blot analysis was utilized to examine the protein levels of resistance markers, Wnt/β-catenin pathway markers and FBN1. The interaction between miR-342-3p and hsa_circ_0004674 or FBN1 was confirmed by dual-luciferase reporter assay and RNA pull-down assay. Moreover, animal experiments were performed to assess the effect of hsa_circ_0004674 silencing on the DXR sensitive of OS in vivo. Results The upregulated hsa_circ_0004674 was found in DXR-resistant OS tissues and cells. Knockdown of hsa_circ_0004674 could inhibit the DXR resistance of OS cells in vitro and promote the DXR sensitive of OS tumors in vivo. In addition, we discovered that hsa_circ_0004674 could sponge miR-342-3p, and miR-342-3p could target FBN1. MiR-342-3p inhibitor could reverse the inhibition effect of hsa_circ_0004674 knockdown on the DXR resistance of OS cells. Similarly, the suppressive effect of miR-342-3p on the DXR resistance of OS cells also could be reversed by FBN1 overexpression. Furthermore, we revealed that hsa_circ_0004674 silencing inhibited the activity of Wnt/β-catenin pathway by the miR-342-3p/FBN1 axis. Conclusion Hsa_circ_0004674 facilitated the DXR resistance of OS through Wnt/β-catenin pathway via regulating the miR-342-3p/FBN1 axis, suggesting that hsa_circ_0004674 was a promising target for the chemoresistance of OS.

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LncRNA LINC00313 Knockdown Inhibits Tumorigenesis and Metastasis in Human Osteosarcoma by Upregulating FOSL2 through Sponging miR-342-3p

Cited by 17 publications

References 28 publications

LINC00313 regulates the metastasis of testicular germ cell tumors through epithelial-mesenchyme transition and immune pathways

LINC00313 regulates the metastasis of testicular germ cell tumors through epithelial-mesenchyme transition and immune pathways

Development of a Machine Learning-Based Autophagy-Related lncRNA Signature to Improve Prognosis Prediction in Osteosarcoma Patients

Hsa_circ_0004674 promotes osteosarcoma doxorubicin resistance by regulating the miR-342-3p/FBN1 axis

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