Downregulation of SCARA5 may contribute to breast cancer via promoter hypermethylation

Ulker, Damla; Ersoy, Yeliz Emine; Güçin, Zühal; Müslümanoğlu, Mahmut; Buyru, Nur

doi:10.1016/j.gene.2018.06.036

Cited by 32 publications

(24 citation statements)

References 24 publications

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“…In this study, SCARA5 overexpression significantly suppressed cell proliferation, colony formation, invasion, and migration, and induced G0/G1 arrest and apoptosis. Recently, another group reported that SCARA5 expression was significantly decreased in tumors (92.2%), compared to non-cancerous tissue samples, due to the hypermethylation of the promoter [33]. There are no reports implicating SCARA5 in PRAD, but based on our results we hypothesize a similar pattern of expression.…”

Section: Discussionsupporting

confidence: 78%

Twiner: correlation-based regularization for identifying common cancer gene signatures

2019

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Background: Breast and prostate cancers are typical examples of hormone-dependent cancers, showing remarkable similarities at the hormone-related signaling pathways level, and exhibiting a high tropism to bone. While the identification of genes playing a specific role in each cancer type brings invaluable insights for gene therapy research by targeting disease-specific cell functions not accounted so far, identifying a common gene signature to breast and prostate cancers could unravel new targets to tackle shared hormone-dependent disease features, like bone relapse. This would potentially allow the development of new targeted therapies directed to genes regulating both cancer types, with a consequent positive impact in cancer management and health economics. Results: We address the challenge of extracting gene signatures from transcriptomic data of prostate adenocarcinoma (PRAD) and breast invasive carcinoma (BRCA) samples, particularly estrogen positive (ER+), and androgen positive (AR+) triple-negative breast cancer (TNBC), using sparse logistic regression. The introduction of gene network information based on the distances between BRCA and PRAD correlation matrices is investigated, through the proposed twin networks recovery (twiner) penalty, as a strategy to ensure similarly correlated gene features in two diseases to be less penalized during the feature selection procedure. Conclusions: Our analysis led to the identification of genes that show a similar correlation pattern in BRCA and PRAD transcriptomic data, and are selected as key players in the classification of breast and prostate samples into ER+ BRCA/AR+ TNBC/PRAD tumor and normal tissues, and also associated with survival time distributions. The results obtained are supported by the literature and are expected to unveil the similarities between the diseases, disclose common disease biomarkers, and help in the definition of new strategies for more effective therapies.

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Section: Discussionsupporting

confidence: 78%

Twiner: correlation-based regularization for identifying common cancer gene signatures

2019

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“…downregulation in cancer can be attributed to a number of molecular mechanisms, including mutation, deletion, hypermethylation and microRNA regulation. Aberrant methylation of CpG islands in the promoter region of genes is a frequent mechanism for their downregulation in cancer (26)(27)(28)(29). Hypermethylation of the CpG island in the EphA5 promoter has been reported in human cancer types (19).…”

Section: Ihc Score (24) ---------------------------------------------mentioning

confidence: 99%

Differential expression of EphA5 protein in gastric carcinoma and its clinical significance

et al. 2019

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The aim of the present study was to evaluate ephrin type-A receptor 5 (EphA5) expression and its clinicopathological significance in gastric cancer. Gastric cancer tissues were analyzed by immunohistochemistry. The association between EphA5 expression and clinicopathological parameters, human epidermal growth factor receptor 2 (HER2) status and Ki-67 proliferation index was statistically analyzed. EphA5 expression was detected in all non-tumor gastric epithelia but was differentially expressed among gastric cancer samples. EphA5 was negatively expressed in 30/110 (27.3%) and positively expressed in 80/110 (72.3%) samples from patients with gastric cancer. EphA5 expression was significantly associated with Lauren classification (P= 0.032), lymph node metastasis (P<0.001), HER2 expression (P=0.020) and Ki-67 expression (P=0.005). No significant association was determined between EphA5 expression and age, sex, primary location, depth of invasion and Tumor-Node-Metastasis stage. The present data indicated that EphA5 is differentially expressed in gastric cancer. EphA5 may therefore be a potential therapeutic target and may have clinical utility as a marker for lymph node metastasis in gastric cancer.

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“…Scavanger receptors (SRs) are a type of receptor superfamily which contains one or several repeats of highly conserved SRCR domain protein module . Many biomolecules such as modified lipoproteins, lipids, polyribonucleotide and polysaccharides are able to combine this membrane receptor . In the previous study, SRs had been divided into eight discrete classes based on their ability to identify different type of low density lipoprotein .…”

Section: Introductionmentioning

confidence: 99%

Scavenger receptor class A, member 5 is associated with thyroid cancer cell lines progression via epithelial‐mesenchymal transition

Zheng

Xia

Quan

et al. 2020

Cell Biochemistry & Function

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Thyroid cancer (TC) has become one of most common endocrine malignancies in recent decades. Due to gene background polymorphism, it's outcome goes quite differently in each patient. For exploring the mechanism, we performed whole transcriptome sequencing of paired papillary thyroid carcinoma (PTC) and adjacent thyroid tissues. As a result, scavenger receptor class A member 5 (SCARA5) might be a crucial anti-oncogene associated with PTC. By RT-qPCR, we first detected the expression of SCARA5 in PTC tissue and three type of TC cell lines. Besides, The Cancer Genome Atlas (TCGA) data were gathered to analysis the relationship between SCARA5 and clinical feature. A series of loss-function experiments in TC cell lines (KTC-1 and BCPAP) to investigate the function of SCARA5 in PTC. The results showed that SCARA5 expression in PTC was lower than adjacent normal tissue. And, it's consistent with the TCGA database. After analyse the correlation between SCARA5 expression and clinicopathological features in TCGA database, we discovered that downregulated SCARA5 is significantly connected age (P = .04) and tumour size (P = .032). Knockdown of SCARA5 in TC cell line could significantly increase the function of cells proliferation, colony formation, migration, and invasion. Furthermore, we also proved that SCARA5 could modulate the expression of epithelial-mesenchymal transition-related proteins, which influence invasion and migration. To best of our knowledge, SCARA5 is a suppressor gene which was associated with PTC and might be a potential therapeutic target in the future.Significance of the study: Thyroid cancer (TC) has become one of most common endocrine malignancies in recent decades. By whole transcriptome sequencing of paired papillary thyroid carcinoma (PTC) and adjacent thyroid tissues, author discovered that scavenger receptor class A member 5 (SCARA5) might be crucial antioncogene associated with PTC. Furthermore, knocking-down of SCARA5 in TC cell line can increase the function of cells proliferation, colony formation, migration, and invasion. Author also proved that SCARA5 could modulate the expression of epithelialmesenchymal transition-related proteins.Ru-Tian Hao and Ou-Chen Wang contributed equally to this study.

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Downregulation of SCARA5 may contribute to breast cancer via promoter hypermethylation

Cited by 32 publications

References 24 publications

Twiner: correlation-based regularization for identifying common cancer gene signatures

Twiner: correlation-based regularization for identifying common cancer gene signatures

Differential expression of EphA5 protein in gastric carcinoma and its clinical significance

Scavenger receptor class A, member 5 is associated with thyroid cancer cell lines progression via epithelial‐mesenchymal transition

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