Expression profile of SYNE3 and bioinformatic analysis of its prognostic value and functions in tumors

Abstract

Background: 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. 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.

Methods: Here, 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.

Results: SYNE3 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.

Conclusions: Our study explored novel anti-tumor functions and mechanisms of SYNE3, which might be useful for future cancer therapy.

Keywords: Bioinformatic analysis; CeRNA network; Expression profile; Immune infiltration; SYNE3; Tumor.

Fig. 1

Gene structure, protein structure and conservative analysis of SYNE3. a Chromosome localization and gene structure of SYNE3 in human. b Structure of nesprin-3ɑ, the most common SYNE3 encoding protein. c Comparison of protein sequences encoded by SYNE3 among six different species. d Phylogenetic tree of SYNE family

Fig. 2

Expression pattern of SYNE3 in BALB/c mice and human. a distribution of SYNE3 in tissues from BALB/c mice (100×; 400×; five samples in each group). b Immunohistochemistry results of SYNE3 performed in both normal and tumor tissues of human (100×; 400×; more than three samples in each group)

Fig. 3

Networks regulating SYNE3. a Result of predicted miRNAs using 4 different database. Hsa-miR-330-3p and hsa-miR-149-5p were finally screened by overlapping these data and the result was visualized on Bioinformatics & Evolutionary Genomics website. b Predicted interaction between miR-149-5p/miR-330-3p and SYNE3. c Construction of ceRNA network of SYNE3. d SYNE3 expression in LUAD according to TCGA database. e Differential expression profile in cancer vs normal of miR-330-3p and miR-149-5p. f LncRNAs in the network differently expressed in normal vs tumor in LUAD based on TCGA database. g Predicted interaction of miR-149-5p–RP11-2B6.2 and miR-330-3p–RP11-67L2.2. h A ceRNA network in LUAD composed of SYNE3, miR-149-5p, miR-330-3p, RP11-2B6.2 and RP11-67L2.2

Fig. 4

Transcriptional network of SYNE3. a predicted SYNE3-associated transcriptional factors based on the results of GCBI online database. b TFs differently expressed in normal tissues and tumor tissues of LUAD. c Pearson correlation coefficient between SYNE3 expression and SATB1 expression. d MiRNA screened to regulate SATB1, using the data of Tarbase, mirDIP, miRWalk and previous analysis. e transcriptional network among SYNE3, miR-149-5p and SATB1 in LUAD

Fig. 5

Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis of SYNE3. a an protein–protein interacting network of SYNE3 constructed with data from STRING. b KEGG enrichment was performed by using KOBAS 3.0 database, and the most enriched pathway map was pictured based on map from KEGG Mapper. c GO analysis was performed with DAVID (Database for Annotation, Visualization and Integrated Discovery) in three aspects: Molecular Function, Biological Process and Cellular Component

Fig. 6

The role SYNE3 played in tumor microenvironment. a Immune infiltration level associated with SYNE3 in HNSC, KIRC and LUAD analyzed in TIMER. b The relationship between immune cell infiltration and lung adenocarcinoma prognosis, higher infiltration level of B cell and dentritic cell were significantly associated with better clinical outcome of LUAD. c Higher SYNE3 expression was correlated with longer OS of patients with lung adenocarcinoma. d SYNE3 expression was significantly downregulated in LUAD compared with that in normal lung tissues. e GSEA analysis grouped by SYNE3 expression level. f The correlation between SYNE3 expression and expression of B cell and dentritic cell based on GEPIA database