TRIM2 regulates the development and metastasis of tumorous cells of osteosarcoma

Abstract

The present study aimed to investigate candidate genes involved in the development and metastasis of osteosarcoma. Candidate genes were screened preliminarily from the Gene Expression Omnibus database and then validated using actual tumor tissues collected from patients with osteosarcoma. The cells were prepared and transfected with specific gene-targeted small interfering RNA followed by an MTS assay for cell viability detection and Transwell assays for cell migration and invasion capacity detection. The cell apoptosis was determined by flow cytometry and the protein level of the genes was detected by western blot analysis. An in vivo nude model was used and injected with cells to detect the functions of the genes. Transcriptome sequencing was performed to verify the regulation network, followed by reverse transcription-quantitative polymerase chain reaction and western blot analyses for validation. Increased tripartite motif-containing protein 2 (TRIM2) was detected in the osteosarcoma tumor tissues compared with normal tissues. The inhibition of TRIM2 induced lower cell viability and cell invasion capacity, and increased the rate of cell apoptosis. Decreased TRIM2 also inhibited the development and metastasis of osteosarcoma in the nude mouse models. The transcriptome sequencing revealed that the regulation of TRIM2 may be correlated with genes, Sirtuin 4, DNA damage inducible transcript 3, cAMP responsive element binding protein 5, G protein-coupled receptor 65 (GPR65) and ADP-ribosyltransferase 5. Western blot analysis indicated that TRIM2 regulated the development and metastasis of osteosarcoma via the phosphoinositide 3-kinase/protein kinase B signaling pathway. Therefore, TRIM2 performs important functions in regulating the development and metastasis of osteosarcoma.

N6-Methyladenosine modification of the TRIM7 positively regulates tumorigenesis and chemoresistance in osteosarcoma through ubiquitination of BRMS1

“…TRIM37 is upregulated in pediatric osteosarcoma tissues, and its overexpression induces cell proliferation and reduces chemosensitivity in osteosarcoma [7] . TRIM2 is increased in osteosarcoma tissues, and its downregulation induces increased cell apoptosis, decreased cell invasion and migration, and inhibition of metastasis in vivo nude mice model of osteosarcoma mice [8] . TRIM14 is upregulated in osteosarcoma tissues and cell lines, and its overexpression promotes tumour growth in vivo and increases osteosarcoma cell cycle procession, clone formation, as well as cell invasion, migration, and proliferation in vitro [9] .…”

“…Although metastasis and chemoresistance are the leading causes of death in osteosarcoma patients, the mechanisms responsible for metastasis and chemoresistance remain unclear. A large body of evidence shows that TRIM family member proteins can function as potential oncogenes or tumour suppressor genes and that these proteins could be used as potential biomarkers for chemoresistance, prediction of prognosis, and diagnosis in various cancers [ 7 , 8 , 28 ]. TRIM7 expression is markedly increased in patients with metastatic osteosarcoma than that in patients without metastasic osteosarcoma, and this increased expression is associated with survival time in patients with osteosarcoma patients.…”

“…The B-box and coiled-coil regions, on the other hand, promote protein-protein interactions and homo-oligomerization [6] . A growing body of evidence now suggests that the TRIM family of proteins can act as tumour suppressors or oncogenes and are involved in osteosarcoma development [7] , [8] , [9] . Analyses from cDNA microarrays have shown that TRIM7 is up-regulated in mucinous colorectal carcinomas compared with non-mucinous colorectal carcinomas [10] .…”

Meta-Analysis of Microarray Expression Studies on Metformin in Cancer Cell Lines

“…Depending on its role in glucose and glutamine metabolism of cancer cells, the transporter can emerge as a target for anticancer treatment. In osteosarcoma, the E3-ubiquitin ligase TRIM2 is implicated in regulating development and metastasis, while its downregulation in clear cell renal cell carcinoma promoted cell proliferation, migration, and invasion and acted as an unfavorable prognostic indicator [26,27]. The acidic protein tuftelin 1 (TUFT1) is involved in mTORC1 activation by interacting with the RAB GTPase activating protein 1 (RABGAP1) and therefore may constitute a biomarker or a candidate for targeted therapy in mTOR activated, progressive cancers [28].…”

A Retrospective Clinicopathological Study of Osteosarcoma Patients with Metachronous Metastatic Relapse

“…Some patients develop metastases during treatment, and they have a poor prognosis which is similar with synchronous distant metastasis. However, patients with metachronous metastatic relapse frequently exists metastasis after standardized treatment especially during the follow-up, which is the main reason for clinical treatment failed 5-7. It is an important step to summarize the characteristics of patients with metachronous metastatic relapse to find more pieces of evidence and clinicopathological characteristics for predicting the outcome of patients after receiving standard treatment.…”