Abstract
BackgroundSpectrin repeat containing nuclear envelope family member 3 (SYNE3) encodes an essential component of the linker of the cytoskeleton and nucleoskeleton (LINC) complex, namely nesprin-3. In a tumor, invasiveness and metastasis rely on the integrity of the LINC complex, while the role of SYNE3/nesprin-3 in cancer is rarely studied.MethodsHere, we explored the expression pattern, prognostic value, and related mechanisms of SYNE3 through both experimental and bioinformatic methods. We first detected SYNE3 in BALB/c mice, normal human tissues, and the paired tumor tissues, then used bioinformatics databases to verify our results. We further analyzed the prognostic value of SYNE3. Next, we predicted miRNA targeting SYNE3 and built a competing endogenous RNA (ceRNA) network and a transcriptional network by analyzing data from the cancer genome atlas (TCGA) database. Interacting genes of SYNE3 were predicted, and we further performed GO and KEGG enrichment analysis on these genes. Besides, the relationship between SYNE3 and immune infiltration was also investigated.ResultsSYNE3 exhibited various expressions in different tissues, mainly located on nuclear and in cytoplasm sometimes. SYNE3 expression level had prognostic value in tumors, possibly by stabilizing nucleus, promoting tumor cells apoptosis, and altering tumor microenvironment. Additionally, we constructed a RP11-2B6.2-miR-149-5p-/RP11-67L2.2-miR-330-3p-SYNE3 ceRNA network and a SATB1-miR-149-5p-SYNE3 transcriptional network in lung adenocarcinoma to support the tumor-suppressing role of SYNE3.ConclusionsOur study explored novel anti-tumor functions and mechanisms of SYNE3, which might be useful for future cancer therapy.
Highlights
Spectrin repeat containing nuclear envelope family member 3 (SYNE3) encodes an essential component of the linker of the cytoskeleton and nucleoskeleton (LINC) complex, namely nesprin-3
Prognostic value of SYNE3 To discover prognostic cancer value of SYNE3, we investigated the connection between SYNE3 expression level and Disease-free survival (DFS) of patients with cancer, finding that higher SYNE3 expression brought longer lifespan to patients with renal clear cell carcinoma (KIRC) (P = 0.033, HR = 0.67) or with cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) (P = 0.046, HR = 0.56) (Additional file 2: Fig. S2a)
Overall, our study firstly provided an overview of SYNE3 expression in diverse normal and tumor tissues
Summary
Spectrin repeat containing nuclear envelope family member 3 (SYNE3) encodes an essential component of the linker of the cytoskeleton and nucleoskeleton (LINC) complex, namely nesprin-3. Invasiveness and metastasis rely on the integrity of the LINC complex, while the role of SYNE3/nesprin-3 in cancer is rarely studied. Tumor malignancies has been greatly endangering public health for a long time. With the development of sequencing technologies, genomic markers are increasingly used in tumor study, including tumor gene mutations and patterns of tumor gene expression. Gene markers can help with judging tumor development process, predicting treatment effect, reducing recurrence rate and mortality, and prolonging survival. Most cancer types have some classic but limited biomarkers which cannot always meet clinical requirements.
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