Abstract
Breast cancer (BC) is one of the most common lethal diseases in women worldwide. Recent evidence has shown that covalently closed Circular RNA (circRNA) deregulation is observed in different human malignancies and cancers. Lately, circRNAs are being considered as a new diagnostic biomarker; however, the mechanism and the correlation of action between circRNAs and BC are still unclear. In the present study, we try to investigate the expression level of hsa_circ_0005046 and hsa_circ_0001791 in BC. By using quantitative real-time polymerase chain reaction (qRT-PCR), expression profiles of candidate circRNAs were detected in 60 BC tissue and paired adjacent normal tissues. Furthermore, the clinicopathological relation and diagnostic value were estimated. Our results showed the higher expression levels of hsa_circ_0005046 and hsa_circ_0001791 in BC tissues compared to paired adjacent normal tissues with P value (P < 0.0001) for both circRNAs, and the area under the receiver operating characteristic (ROC) curve was 0.857 and 1.0, respectively; in addition, a total 10 miRNAs that can be targeted by each candidate circRNAs was predicted base on bioinformatics databases. Taken together, for the first time, the results of our study presented high expression levels of hsa_circ_0005046 and hsa_circ_00017916 in BC; although there was no direct correlation between the high expression level of both circRNAs with clinic pathological factors, except hsa_circ_0001791 association with estrogen receptors (ER), high ROC curve in expressed samples indicated that both circRNAs could be used as a new diagnostic biomarker for BC. Moreover, miRNAs selection tools predicted that miR-215 and mir-383-5p which have a tumor suppressor role in BC can be targeted by our candidate circRNAs to affect the PI3K/AKT pathway; in conclusion, further studies are required to validate the oncogene role of our candidate circRNAs through the PI3k pathway.
Highlights
It has been the most serious malignant tumor for women in developed and developing countries featured with the accumulation of mutations that result in the uncontrolled growth of Breast cancer (BC) tissues [2]. e major risk factors that influence information and development of BC include genetic risk factors, family history, female gender, age, alcohol, and race [3]
High-throughput RNA sequencing studies identified a large number of covalently closed Circular RNAs, a new class of noncoding RNAs, which generated from back splicing and could escape from exonuclease-mediated degradation and more stable in blood or plasma compared to linear RNAs. is characterization has made circRNAs the best candidate for a new diagnostic or prognostic biomarker for cancers, such as BC [6, 7]
We investigate the high expression level of hsa_circ_0005046 and hsa_circ_0001791 by using quantitative real-time polymerase chain reaction (qRT-polymerase chain reaction (PCR)) in 60 BC tissues compared to the paired adjacent tissues (P value 0.0001), and receiver operating characteristic (ROC) curve results indicated that the sensitivity and specificity of the assay were within the acceptable range (AUC 0.77) for hsa_circ_0005046 and (AUC 1.0) for hsa_circ_0001791, so they might be considered as new biomarkers
Summary
Breast cancer (BC) is the most occurring cancer leading to death among women around the world, with more than two million new BC cases in females of all ages detected in 2020 [1].It has been the most serious malignant tumor for women in developed and developing countries featured with the accumulation of mutations that result in the uncontrolled growth of BC tissues [2]. e major risk factors that influence information and development of BC include genetic risk factors, family history, female gender, age, alcohol, and race [3].BC treatment is multidisciplinary, and despite surgical treatment and irradiation, chemotherapy remains one of the important means to treat BC; chemotherapy improved with combinations of adjuvant treatment such as taxane and a new targeted drug such as liposomal anthracyclines is among the most effective treatments for patients with BC [4, 5]. the diagnosis methods and therapy strategies for BC are developing, mortality from thisJournal of Oncology cancer is still significant. erefore, a better understanding of genetic changes in BC can help us to find related molecular mechanisms and genetic markers in prognosis and targeted therapy [6]. Breast cancer (BC) is the most occurring cancer leading to death among women around the world, with more than two million new BC cases in females of all ages detected in 2020 [1]. It has been the most serious malignant tumor for women in developed and developing countries featured with the accumulation of mutations that result in the uncontrolled growth of BC tissues [2]. Previous studies have shown that there is a close correlation between circRNAs and initiation and progression of different cancers and diseases; knowledge about the correlation between noncoding RNAs, especially the circRNAs and BC, is not fully explored [7, 8] High-throughput RNA sequencing studies identified a large number of covalently closed Circular RNAs (circRNAs), a new class of noncoding RNAs, which generated from back splicing and could escape from exonuclease-mediated degradation and more stable in blood or plasma compared to linear RNAs. is characterization has made circRNAs the best candidate for a new diagnostic or prognostic biomarker for cancers, such as BC [6, 7].
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