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BAHD1 serves as a critical regulator of breast cancer cell proliferation and invasion

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A Correction to this article was published on 16 September 2022

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Abstract

Breast cancer patients with lymphatic metastasis suffer from poor prognoses. There is an urgent need for controlling lymph node metastasis, but it has proven challenging so far. Here, we implemented LASSO analysis of The Cancer Genome Atlas database to identify genes related to lymph node metastasis and prognosis, and 15 genes were selected. We constructed a functional protein association network and univariate Cox regression to identify significant genes. The results showed that BAHD1 could be predictive of lymph node metastasis as well as prognosis. In vitro studies demonstrated that BAHD1 exerted appreciable effects on the proliferation, migration, and invasion capacity of breast cancer cells. Furthermore, downregulation of BAHD1 induced cell cycle arrest in G1 phase. Additionally, the mRNA levels of CCND1, CDK1 and YWHAZ were decreased upon BAHD1 silencing. These findings indicate that the expression of BAHD1 is essential in the progression of breast cancer, which may provide novel therapeutic and diagnostic clues and insights into the prevention of lymph node metastasis in breast cancer.

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All data generated or analyzed in this study are provided in the article and its supplementary files.

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Acknowledgements

Special thanks to Dr. Wang Yang and Dr. Ya Xiao for guidance in data analysis and preparation of the manuscript. We thank Shanghai Outdo Biotech for assistance in sample collection and tissue microarray production.

Funding

This work was supported by Grants from the General Project of Chongqing Natural Science Foundation (Grant no. csts2020jcyj-msxmX0668) and Medical Technology Innovation Fund of Chongqing General Hospital (Y2020ZDXM05).

Author information

Authors and Affiliations

Authors

Contributions

Designed the research: HC, and FZ; acquisition of data: ZY and SY; analysis and interpretation of data: ZY and SY; collection of tissue microarray: QR, DL, YL, TY and JZ; pathological evaluation of tissues: QR, TT; draft of the manuscript: ZY and SY; critical revision of the manuscript: HM and YS; funding acquisition: FZ and SY. All authors read, revised and approved the final manuscript.

Corresponding authors

Correspondence to Fan Zhang or Hongdan Chen.

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The authors declare no potential conflicts of interest.

Ethics approval and consent to participate

Ethics approval of the project was granted by the Medical Ethics Committee from the Shanghai Outdo Biotech Company. Written informed consent was obtained from all patients.

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Consent for publication was obtained from all authors.

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Supplementary Information

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12282_2022_1333_MOESM1_ESM.jpg

Figure S1. Advanced Scarff-Bloom-Richardson grade of breast cancer tissues. A According to the advanced Scarff-Bloom-Richardson grade rules, tissues were graded by histological features of miotic figure, cellular atypia and duct formation (A-E). The scores of each representative figure were 3(A), 4(B), 6(C), 7(D), 8(E). F. Advanced Scarff-Bloom-Richardson grade scores of all the samples. G. Association of BAHD1 expression and advanced Scarff-Bloom-Richardson grade scores. (JPG 1833 kb)

12282_2022_1333_MOESM2_ESM.jpg

Figure S2. Survival analysis based on the gene expression profile in TCGA-BRCA. A. Kaplan–Meier and log-rank tests showing the overall survival curves of patients stratified by the expression of BAHD1, UBQLN1, CAB39L, YBX2, HIST3H2BB, UNC93B1, SLC20A2, BLVRA, SPPL2C, FAM26D, RGPD6, CTRL, GDF5, HIF1A and CDH19. B. Kaplan–Meier and log-rank tests showing the disease-free survival curves of the 15 selected genes. (JPG 483 kb)

12282_2022_1333_MOESM3_ESM.jpg

Figure S3. Survival analysis of BAHD1 in subtypes of breast cancer. A. Kaplan–Meier and log-rank tests showing the overall survival curves of patients stratified by the expression of BAHD1 in luminal subtype breast cancer; B. Kaplan–Meier and log-rank tests showing the overall survival curves of patients stratified by the expression of BAHD1 in triple negative breast cancer; C. Kaplan–Meier and log-rank tests showing the overall survival curves of patients stratified by the expression of BAHD1 in HER2-positive breast cancer. (JPG 196 kb)

12282_2022_1333_MOESM4_ESM.jpg

Figure S4. Differential expression of transcriptome sequencing. A. Box plot of the gene expression distribution according to transcriptome sequencing; B-C. Volcano plots showing differentially expressed genes in the NC and si-BAHD1 groups based on transcriptome sequencing of MCF-7 (B) and MDA-MB-231 cells (C). D. Pathway and process analysis generated by Metascape (https://metascape.org/gp/) of the DEGs. (JPG 490 kb)

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Figure S5. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes in the cell cycle process. (JPG 867 kb)

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Yang, Zy., Yin, Sp., Ren, Q. et al. BAHD1 serves as a critical regulator of breast cancer cell proliferation and invasion. Breast Cancer 29, 516–530 (2022). https://doi.org/10.1007/s12282-022-01333-5

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