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

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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.
Funding Information
  • National Natural Science Foundation of China (81602685, 81672992)
  • Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education (LC2019ZD008)
  • Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical Animal Diseases (2018CR021)
  • Guangzhou Municipal Research Collaborative Innovation Projects (201803040003)
  • Natural Science Foundation of Guangdong Province (2017A030313486)
  • Guangzhou Science and Technology Plan Project (201707010025)
  • CAMS Innovation Fund for Medical Sciences (2016-I2M-1-017, 2017-I2M-B&R-13)

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