Rhomboid family gene expression profiling in breast normal tissue and tumor samples

Canzoneri, Romina; Lacunza, Ezequiel; Larrain, M. Isla; Croce, María Virginia; Abba, Martı́n C.

doi:10.1007/s13277-013-1199-8

Cited by 16 publications

(16 citation statements)

References 30 publications

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“…RHBDD2 overexpression was initially described by Abba et al in patients with advanced breast cancer as a consequence of gene amplification events (3). Recently, we described a significant association between RHBDD2 overexpression among breast carcinomas with low/negative progesterone receptor expression (6). In the present study, we demonstrated that RHBDD2 mRNA variants and their coding proteins can be differentially detected in breast tumor and normal specimens.…”

Section: Discussionsupporting

confidence: 69%

“…In the present study, we demonstrated that RHBDD2 mRNA variants and their coding proteins can be differentially detected in breast tumor and normal specimens. As previously described (3,4,6), total RHBDD2 (mRNA and protein) was found to be upregulated in breast carcinomas. However, individual splicing variant analysis allowed us to detect a significant increment in RHBDD2-2 variant expression in breast carcinomas in respect to normal tissues.…”

Section: Discussionsupporting

confidence: 69%

“…RHBDD2 pseudoprotease has been found overexpressed in advanced-stage breast and colorectal cancers (3)(4)(5)(6). Although the particular RHBDD2 function has not yet been assessed, its expression has been associated with breast cancer cell migration, proliferation, and cellular response to ER stress (7).…”

Section: Introductionmentioning

confidence: 99%

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Alternative splicing variant of RHBDD2 is associated with cell stress response and breast cancer progression

et al. 2018

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RHBDD2 is an intramembrane pseudoprotease member of the Rhomboid superfamily. Our previous studies in breast and colorectal cancer indicate an association between RHBDD2 overexpression and advanced tumor stages. Two alternative transcriptional variants have been described for RHBDD2, which would be encoding for different RHBDD2 protein isoforms. The expression of these RHBDD2 variants/isoforms and its association with breast cancer was the focus of this study. First, expression of RHBDD2 splicing variants was evaluated in normal and breast tumor samples. RHBDD2 variant 2 overexpression was detected in tumors in respect to normal breast tissues at the mRNA and protein levels (P<0.05). Moreover, RHBDD2 variant 2 expression was associated with poor prognostic factors such as basal‑like intrinsic subtype (P<0.05), high proliferation (P<0.01) and long‑term risk‑of‑recurrence (P<0.01) scores. Second, the expression of both variants was evaluated under nutritional‑deprived conditions in breast cancer cell lines. Results demonstrated that RHBDD2 splicing was switched from mRNA variant 1 to variant 2 in association with a significant increment of protein isoform B in response to glucose starvation treatment. Therefore, we propose that the switch from the RHBDD2 variant 1, expressed in normal epithelial cells, to variant 2 occurs as an adaptive phenotype to bypass the stressful tumor microenvironment and promote tumor progression. Finally, the RHBDD2 subcellular localization was corroborated at the Golgi apparatus and their associated v‑SNARE transport vesicles, suggesting a putative new role for RHBDD2 in the protein trafficking of human breast cancer cells.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionsupporting

confidence: 69%

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Alternative splicing variant of RHBDD2 is associated with cell stress response and breast cancer progression

et al. 2018

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“…A prior report showed that RHBDF1 expression is highly elevated in breast cancer and strongly correlated with increased disease progression, metastasis, poor prognosis, and poor response to chemotherapy [26]. RHBDD2 mRNA and protein are overexpressed in breast cancer [27]. Based on these results, we propose that RHBDD1, a member of Rhomboids, may play a role in colorectal cancer by interacting with EGFR.…”

Section: Introductionmentioning

confidence: 56%

RHBDD1 upregulates EGFR via the AP-1 pathway in colorectal cancer

et al. 2017

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Our previous study showed that RHBDD1 can activate the EGFR signaling pathway to promote colorectal cancer growth. In the present study, EGFR was decreased when RHBDD1 was knocked down or inactivated. Further analysis found that c-Jun and EGFR protein expression was decreased in RHBDD1 knockdown and inactivated cells. c-Jun overexpression in RHBDD1-inactivated cells rescued EGFR expression in a dose-dependent manner. RHBDD1 overexpression in RHBDD1-inactivated cells restored EGFR expression, but this effect was counteracted by c-Jun knockdown. Furthermore, EGFR and c-Jun were attenuated in the RHBDD1 knockdown and inactivated groups in animal tumor models. Tissue microarray assays demonstrated a correlation between RHBDD1 and EGFR in colorectal cancer patients. Therefore, our findings indicate that RHBDD1 stimulates EGFR expression by promoting the AP-1 pathway.

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“…RHBDD2 expression has been related to proliferation, migration, and cellular response to ER stress 8 . Over-expression RHBDD2 has also a significant association among breast carcinomas with low-negative progesterone receptor expression 9 . RHBDD2 also involved in ER stress but its specific role is not cleared 10 .…”

Section: Introductionmentioning

confidence: 98%

Transcription Factors STAT5A and SPI1 Reveals RHBDD2 as a Potential Biomarker in Sepsis and Septic Shock

Ali

Shehwana

Hanif

et al. 2020

Preprint

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Sepsis is a serious health situation caused by uncontrolled infection and septic shock is a severe condition of sepsis. RHBDD2 is a member of the rhomboid superfamily which is overexpressed in different types of cancer and associated with ER stress and estrogen receptor. Using microarray gene expression data and using different computational techniques this study investigated the role of RHBDD2 in sepsis and septic shock. Finds functional annotation of RHBDD2 using co-expression analysis and identified the deregulation of RHBDD2 in sepsis using differential expression analysis. Results show that RHBDD2 is overexpressed in sepsis and septic shock. The GO enrichment analysis, KEGG pathways, and biological functions of the RHBDD2 co-expressed genes module show that it is involved in most of the sepsis-related biological functions and also plays a role in most of the infection-related pathways which lead to sepsis and septic shock. RHBDD2 is regulated by STAT5A and SPI1 transcription factors in sepsis and septic shock. The identification of the RHBDD2 as a biomarker may facilitate in septic shock diagnosis, treatment, and prognosis.

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Rhomboid family gene expression profiling in breast normal tissue and tumor samples

Cited by 16 publications

References 30 publications

Alternative splicing variant of RHBDD2 is associated with cell stress response and breast cancer progression

Alternative splicing variant of RHBDD2 is associated with cell stress response and breast cancer progression

RHBDD1 upregulates EGFR via the AP-1 pathway in colorectal cancer

Transcription Factors STAT5A and SPI1 Reveals RHBDD2 as a Potential Biomarker in Sepsis and Septic Shock

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