Comparative expression analysis of hypoxia‐inducible factor‐alpha and its natural occurring antisense in breast cancer tissues and adjacent noncancerous tissues

Abstract

Hypoxia-inducible factors (HIFs) have been shown to be upregulated in tumor tissues and linked with tumor progression and metastasis in breast cancer. Among regulatory mechanisms for HIF expression is a natural occurring antisense named aHIF, which has been shown to be overexpressed in breast cancer and influence the level of the HIF-1α transcript. In the present study, we analyzed the expression of HIF-1α and aHIF in breast cancer tissues versus adjacent noncancer tissues (ANCTs) in relation with the clinical and biological behavior of the tumors. aHIF has been shown to be expressed in 67.4% of invasive ductal carcinoma samples, while none of ANCTs showed its expression. HIF-1α has been expressed in all of tumors and 90% of ANCTs. Comparison of HIF-1α expression level between tumor and ANCT tissues showed a total upregulation in tumor samples. No statistically significant association has been found between the level of HIF-1α expression in tumor samples and clinicopathologic and demographic characteristics such as age, tumor size, estrogen receptor status, progesterone receptor status, HER2/neu expression level, lymph node status, histological grade, and stage except for a weak correlation between HIF-1α expression and Ki-67 status. Besides, we could not detect any significant correlation between relative expression of HIF-1α and aHIF in tumor samples. Collectively, these data suggest that aHIF overexpression can be used as a potential biomarker in breast cancer. However, further studies are needed for the evaluation of its mechanism of action in regulation of HIF-1α expression in different pathological conditions. HIF-1α overexpression results in the upregulation of several genes that participated in cancer-associated pathways such as proliferation, angiogenesis, and glucose metabolism. We showed that HIF-1α is upregulated in breast tumor samples compared with adjacent noncancerous tissues. Its expression has been associated with Ki-67 status. Its natural occurring antisense is only expressed in tumor tissues. Thus, it can be used as a potential biomarker in breast cancer.

Long non-coding RNA GHET1 Is Possibly Involved in the Pathogenesis of a Fraction of Breast Cancers

“…Statistical analyses performed for these 3 groups showed no significant association between GHET1 transcript levels and clinicopathological data. As the expression analyses have been performed on the same samples as our previous study, we further analyzed the associations between GHET1 expression and 2 other lncRNAs, whose expressions have been evaluated in the same samples previously by our group (16). A significant association has been found between GHET1 and CCAT2 expression (P = 0.038), while no association was detected between the levels of GHET1 and aHIF transcripts (P = 0.415).…”

“…were drawn from our previous study (16) and recruited in the current project. Clinicopathological data such as patients' age, tumor size, tumor stage and grade, ER, PR, Her2/neu, and Ki67 status have been investigated based on the evidences acquired from questionnaires, interviews,…”

“…In addition, they have been shown to participate in many central biologic processes comprising regulation of gene expression, telomere length, chromatin reorganization, histone alterations, genomic imprinting, and cell differentiation all of them being involved in cancer development (14,15). We have previously evaluated the expression of a number of lncRNAs in breast cancer in relation to patients' clinical characteristics to determine the role of these transcripts in breast tumorigenesis (16,17). In the present study, we aimed at identifying lncRNA-gastric carcinoma high ex-pressed transcript 1 (lncRNA-GHET1, AK123072) expression in breast cancer tissues compared with their adjacent noncancerous tissues (ANCT) in a cohort of Iranian patients.…”

Expression analysis of selected miR‐206 targets from the transforming growth factor‐β signaling pathway in breast cancer

“…Breast cancer as the most worldwide prevalent cancer among women is associated with aberrant expression of several messenger RNA (mRNA) coding genes, microRNAs (miRNAs) as well as long noncoding RNAs . In addition, dysregulation of several signaling pathways is implicated in breast cancer pathogenesis.…”

MiR-206 Target Prediction in Breast Cancer Subtypes by Bioinformatics Tools

“…Several researches have focused on the exploration of gene expression patterns among these subtypes to find a biologically relevant biomarker in breast cancer (2)(3)(4)(5). The expression pattern analysis of noncoding RNAs has also been the focus of researchers (6,7). Pathway-based expression analysis has further been suggested as a more systematic strategy for biomarker discovery (8,9).…”