Редактирование: P4HA3 (раздел)

==Publications==

{{medline-entry
|title=Age-associated genes in human mammary gland drive human breast cancer progression.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32539762
|abstract=Aging is a comorbidity of breast cancer suggesting that aging-associated transcriptome changes may promote breast cancer progression. However, the mechanism underlying the age effect on breast cancer remains poorly understood. We analyzed transcriptomics of the matched normal breast tissues from the 82 breast cancer patients in The Cancer Genome Atlas (TCGA) dataset with linear regression for genes with age-associated expression that are not associated with menopause. We also analyzed differentially expressed genes between the paired tumor and non-tumor breast tissues in TCGA for the identification of age and breast cancer (ABC)-associated genes. A few of these genes were selected for further investigation of their malignancy-regulating activities with in vitro and in vivo assays. We identified 148 upregulated and 189 downregulated genes during aging. Overlapping of tumor-associated genes between normal and tumor tissues with age-dependent genes resulted in 14 upregulated and 24 downregulated genes that were both age and breast cancer associated. These genes are predictive in relapse-free survival, indicative of their potential tumor promoting or suppressive functions, respectively. Knockdown of two upregulated genes ([[DYNLT3]] and [[P4HA3]]) or overexpression of the downregulated [[ALX4]] significantly reduced breast cancer cell proliferation, migration, and clonogenicity. Moreover, knockdown of [[P4HA3]] reduced growth and metastasis whereas overexpression of [[ALX4]] inhibited the growth of xenografted breast cancer cells in mice. Our study suggests that transcriptome alterations during aging may contribute to breast tumorigenesis. [[DYNLT3]], [[P4HA3]], and [[ALX4]] play significant roles in breast cancer progression.
|mesh-terms=* Adult
* Age Factors
* Aged
* Aged, 80 and over
* Animals
* Biomarkers, Tumor
* Breast
* Breast Neoplasms
* Disease Progression
* Dyneins
* Female
* Gene Expression Regulation, Neoplastic
* Heterografts
* Humans
* Mice
* Mice, Inbred NOD
* Mice, SCID
* Middle Aged
* Procollagen-Proline Dioxygenase
* Prognosis
* Survival Rate
* Tumor Cells, Cultured
|keywords=* ALX4
* Aging
* Breast cancer
* DYNLT3
* Gene expression
* P4HA3
* Relapse-free survival
* Transcriptomics
* Tumor progression
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294649
}}