DSG2 and c-MYC Interact to Regulate the Expression of ADAM17 and Promote the Development of Cervical Cancer

Figures & data

Figure 1 DSG2 is up-regulated in human cervical cancer and is associated with a poor prognosis. (A) Higher expression of DSG2 was found in cervical cancer samples than the normal tissues (based on TCGA database). (B) Kaplan–Meier plots of overall survival for cervical cancer samples with high/low DSG2 expression from the TCGA database.

Figure 2 Knockdown of DSG2 in cervical cancer cells. (A) The knockdown efficiency of the three groups of siRNA in HeLa cells was 84%, 86% and 28%, respectively. (B and C) The specificity and validity of the siRNA knockdown of DSG2 expression in HeLa and SiHa cells was verified by qPCR (B) and WB (C). *P < 0.05, **P < 0.01.

Figure 3 Knockdown of DSG2 inhibited proliferation and migration of cervical cancer cells. (A) The proliferation of HeLa and SiHa cells after knockdown of DSG2 was measured using CCK-8 assay. (B) The effect of DSG2 knockdown on cervical cancer cell clone formation. (C) The migration ability of HeLa and SiHa cells after knockdown of DSG2 was measured using Transwell assay. *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 4 ADAM17 is up-regulated in human cervical cancer and is associated with a poor prognosis. (A) The bioinformatics analysis of TCGA-CHOL dataset showed the positive expression correlation between DSG2 and ADAM17. (B) Higher expression of ADAM17 was found in cervical cancer samples than the normal tissues (based on TCGA database). (C) Kaplan–Meier plots of overall survival for cervical cancer samples with high/low ADAM17 expression from the TCGA database.

Figure 5 DSG2 regulates the expression of ADAM17 in cervical cancer. (A) The effect of DSG2 knockdown on ADAM17mRNA expression was detected by qPCR. (B) The effect of DSG2 knockdown on ADAM17 protein expression was detected by WB. (C) The interaction between DSG2 and c-MYC was detected by Co-IP assay. ***P < 0.001.

Figure 6 DSG2 regulates cervical cancer development by interacting with c-MYC. (A) HeLa cells were transfected with pcDNA(3.1)-DSG2 overexpression plasmid, and the mRNA level of DSG2 was detected by qPCR. (B) HeLa cells were transfected with pcDNA(3.1) overexpression plasmid, and the protein level of DSG2 was detected by WB. (C and D) DSG2 overexpressed HeLa cells were treated with a C-MYC inhibitor (10,058-F4, 50 μM), and the proliferative activity and migration ability were detected by CCK-8 (C) and clonal formation assay (D). (E) DSG2 overexpressed HeLa cells were treated with a C-MYC inhibitor, and ADAM17 protein expression was detected by WB.*P < 0.05, **P < 0.01, ***P < 0.001.