LIM domain-containing 2 (LIMD2) promotes the progress of ovarian cancer via the focal adhesion signaling pathway

Abstract

Ovarian cancer (OC) is the leading cause of death from gynecological cancer. In this study, we aimed to explore the role and potential mechanism of LIMD2 during the progression of OC. The expression of LIMD2 was analyzed by GEPIA (Gene Expression Profiling Interactive Analysis) database. Western blot and real-time PCR were applied to detect the gene expression of LIMD2 in OC cell lines. Cell counting kit-8 (CCK-8) assay, transwell, wound healing assays, and tumor xenograft experiments were used to evaluate the function of LIMD2 in vitro and vivo . Further, the LIMD2-associated pathways in OC were predicted by RNA-seq analysis, and the involvement of the corresponding cell signaling activities were confirmed by Western blot. We found that LIMD2 was high expressed in OC. Additionally, we found that silencing of LIMD2 inhibited OC cell proliferation in vitro and reduced the growth of its xenograft tumors. Moreover, knockdown of LIMD2 significantly decreased the migration of OC cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that pathways regulating extracellular matrix (ECM)-receptor interactions and focal adhesion signaling, were deregulated by LIMD2. Particularly, we confirmed that reducing LIMD2 could decrease the expression of Focal adhesion kinase (FAK) pathway related molecules. In conclusion, LIMD2 promotes the proliferation and invasion of ovarian cancer in vitro and in vivo , potentially through regulating the focal adhesion signaling pathway.

Chromosome instability region analysis and identification of the driver genes of the epithelial ovarian cancer cell lines A2780 and SKOV3

“…In both cell lines, we found significantly KEGG‐defined pathways, including ECM‐receptor interaction, ABC transporters, Notch signalling pathway, etc. The ECM‐receptor interaction route has been linked to OC in existing studies, 23 and many important genes also have an impact on the growth of the disease through this pathway 24–26 . The Notch signalling pathway, which is also crucial for most tissue determination and development, is dysregulated in solid tumours and human malignancies 27–29 .…”

“…The ECM-receptor interaction route has been linked to OC in existing studies, 23 and many important genes also have an impact on the growth of the disease through this pathway. [24][25][26] The Notch signalling pathway, which is also crucial for most tissue determination and development, is dysregulated in solid tumours and human malignancies. [27][28][29] Variations in several of these pathway genes were also discovered by integrated and epigenomic analyses of OC cell lines.…”

ANXA5 promotes glioma progression through the FAk/PI3K/AKT pathway

“…Focal adhesion is mediated macromolecular complex extracellular matrix interaction, by integrin receptor to connect focal adhesion related proteins to actin cytoskeleton [36]. FAK, a non-receptor tyrosine kinase laid in the integrin aggregation region, is the hub of the focal adhesion interactome and affects tumor cell proliferation and motility by regulating multiple signaling pathways [37,38]. FAK consists of three domains, among which Y397 located in the N-terminal FERM region is the most important site for FAK autophosphorylation, and the phosphorylated FAK is in the activated state [39].…”