title: 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.
authors.affiliation: Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Behnoosh
authors.initials: B
authors.lastname: Tasharrofi
authors.affiliation: Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Soudyab
authors.affiliation: Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Elahe
authors.initials: E
authors.lastname: Nikpayam
authors.affiliation: Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Iranpour
authors.affiliation: Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Mirfakhraie
authors.affiliation: Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Shaghayegh
authors.initials: S
authors.lastname: Sarrafzadeh
authors.affiliation: Department of Surgery, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Lobat
authors.initials: L
authors.lastname: Geranpayeh
authors.affiliation: Department of Social Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Eznollah
authors.initials: E
authors.lastname: Azargashb
authors.affiliation: Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Arezou
authors.initials: A
authors.lastname: Sayad
authors.affiliation: Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Soudeh
authors.initials: S
authors.lastname: Ghafouri-Fard
mesh_terms: D000293:Adolescent; D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics*; D002648:Child; D003710:Demography; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D016372:RNA, Antisense / Q000235:genetics* / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016372:RNA, Antisense
keywords: HIF-1α; aHIF; breast cancer; long noncoding RNA