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. 2021 Feb 24:11:582277.
doi: 10.3389/fonc.2021.582277. eCollection 2021.

DNAJC12 as a Mediator Between ESR1 and ERBB4 in Breast Carcinoma Cells

Mianjie Lin  1 , Ya-Nan Wang  2 , Yixin Ye  2 , Zhelei Xiong  2 , Fengbiao Guo  2 , Haibin Chen  1   2
Affiliations

DNAJC12 as a Mediator Between ESR1 and ERBB4 in Breast Carcinoma Cells

Mianjie Lin et al. Front Oncol. .

Abstract

Mutation of the DNAJC12 gene is typically associated with non-progressive Parkinsonism, but is also detectable in breast carcinoma where its contribution and mechanisms are unexplored. In breast carcinoma, ESR1 was positively correlated with DNAJC12 and ERBB4, and DNAJC12 was positively correlated with ERBB4. We used the GEO2R tool to compare differential gene expression of MCF-7 cells, following ESR1 knockdown (GEO database, E-GEOD-27473 array), and found decreased expression of DNAJC12 and ERBB4 in ESR1-silenced MCF-7 cells. The number of identical genes having correlativity with ESR1, DNAJC12, or ERBB4 was 12,165 (66.41%). These results suggest that ESR1 can promote the expression of DNAJC12 and ERBB4, and DNAJC12 can enhance the expression of ERBB4 in MCF-7 cells, implying that there may be a regulatory network among these three genes.

Keywords: DNAJC12; ERBB4; ESR1; breast carcinoma; signaling pathway.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Predicted ESR1 binding sites. The first base to the 2,000th base is DNAJC12 promoter, the red underlined areas and blue underlined areas were both predicted ESR1 binding sites.
Figure 2
Figure 2
Effect of ESR1 protein overexpression on the expression of DNAJC12 protein and ERBB4 protein. (A) MCF-7 cells were transfected with ESR1 plasmids and at 0, 24, 48, and 72 h after transfection, western blotting was performed to detect protein expression of ESR1 and DNAJC12 (n = 5). (B) Bar chart of ESR1 protein expression level. (C) Bar chart of DNAJC12 protein expression. (D) MCF-7 cells were transfected with ESR1 plasmids, and at 0, 24, 48, and 72 h after transfection, western blotting was performed to detect expression of ERBB4 (n = 3). (E) Bar chart of ERBB4 protein expression. (*P < 0.05, **P < 0.01, ****P < 0.0001).
Figure 3
Figure 3
Effect of DNAJC12 overexpression on expression of various genes. (A) MCF-7 cells were transfected with DNAJC12 plasmids, and then the mRNA of various genes was detected by PCR at 0, 24, 48, and 72 h (n = 3). (B) DNAJC12 mRNA expression. (C) APH1B mRNA expression. (D) CCNE1 mRNA expression. (E) IGF1R mRNA expression. (F) BCL2 mRNA expression. (G) ERBB4 mRNA expression. (H) MCF-7 cells were transfected with DNAJC12 plasmids, and then western blotting was used to detect the protein expression levels of DNAJC12 and ERBB4 at 0, 24, 48, and 72 h (n = 5). (I) DNAJC12 protein expression. (J) ERBB4 protein expression. (*P < 0.05, **P < 0.01, ***P < 0.001).
Figure 4
Figure 4
Analysis of breast carcinoma samples from the TCGA database. (A) Relational diagram between mRNA expression levels of ESR1 and DNAJC12. (B) Relational diagram between mRNA expression levels of ESR1 and ERBB4. (C) Relational diagram between mRNA expression levels of DNAJC12 and ERBB4. (D) Venn diagram of genes having correlativity with ESR1, DNAJC12, and ERBB4. The flesh color circle represents genes having correlativity with ESR1, the pink circle represents genes having correlativity with DANJC12, and the claybank circle represents the genes having correlativity with ERBB4.
Figure 5
Figure 5
Relationship network diagram among some genes, including ESR1, DNAJC12, and ERBB4.
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