Upregulation of SOX18 in colorectal cancer cells promotes proliferation and correlates with colorectal cancer risk

Abstract

BackgroundSince colorectal cancer (CRC) is one of the most common malignant tumors worldwide, we aimed to identify the role of sex determining region Y (SRY)-box 18 (SOX18) in CRC.MethodsRT-PCR and immunohistochemistry were employed to detect the expression of SOX18 in CRC samples. We then identified the effect of SOX18 on cell proliferation, cell cycle, and apoptosis by cell counting kit-8 (CCK-8), flow cytometry, and annexin V/PI staining, respectively. The effect of silencing SOX18 expression in CRC development was evaluated by using a xenograft mouse model.ResultsFirst, we found that SOX18 was overexpressed in CRC tissues and cell lines and that SOX18 levels in CRC tissues were positively associated with advanced clinical stages, vascular invasion, and lymph node metastasis. Furthermore, patients with higher expression of SOX18 had a lower survival rate. Overexpression of SOX18 significantly promoted cell proliferation, promoted S cell cycle progression, and inhibited cell apoptosis. Conversely, downregulation of SOX18 clearly weakened cell proliferation, induced G0/G1 cell cycle phase arrest, and gave rise to cell apoptosis. The results showed that shSOX18 significantly inhibited tumor growth and weight. Ki67 expression was also decreased by SOX18 silencing treatment.ConclusionOur study indicates that SOX18 may have a carcinogenic effect on CRC, which might provide novel insights into CRC prevention and treatment.

EGR1 Enhances Lymphangiogenesis via SOX18-Mediated Activation of JAK2/STAT3 Pathway

“…SOX18 is one of the members of the Sox subfamily, which has a crucial function in the formation of lymphatic network [ 22 ]. Using molecular, cellular, and genetic assays, SOX18 is shown to be important for the differentiation of lymphatic endothelial cells in mice [ 32 ].…”

“…SOX18 is one of the members of the SOX subfamily, which plays an important role in cell differentiation and cell survival during embryonic development [ 21 ]. SOX18 has a crucial function in the formation of lymphatic network [ 22 ]. It has been demonstrated that SOX18 promotes lymphatic vessel formation in both embryogenesis and tumor-induced lymphangiogenesis [ 23 ].…”

The Impact of Transcription Factor Prospero Homeobox 1 on the Regulation of Thyroid Cancer Malignancy

“…VEGFD can induce both intra-and peri-tumoral lymphatic vessel development; however, it is not involved in lymph node metastasis [29]. Finally, a series of lymphatic factors, including PROX1, VEGFC, PDPN, VEGFR-3, SOX18 (SRY-Box transcription factor 18), and COUP-TFII (Nuclear receptor subfamily 2 group F member 2) can be expressed in tumoral cells and, consequently, control their properties, such as invasion, migration, proliferation, survival, epithelial to mesenchymal transition (EMT), and adhesion [30][31][32][33][34][35].…”

Long non-coding RNA DUXAP10 exerts oncogenic properties in osteosarcoma by recruiting HuR to enhance SOX18 mRNA stability

“…Sex-determining region Y-box 18 (SOX18) is a member of the sex-determining region of the Y-chromosome-related high-mobility group box (SOX) family of transcription factor. There are some studies have reported that SOX18 functioned as an oncogene in tumors by regulating cell cycle and apoptosis [ 42 – 44 ]. However, its molecule mechanism in osteosarcoma has not yet been discovered [ 45 , 46 ].…”