Upregulation of circular RNAs circCSPP۱,circNRIP۱, and circSMAD۲ and association with clinicopathologiccharacteristics in breast cancer

Background: Breast cancer is the most common malignancyand leading cause of mortality due to cancer in women. Novelbiomarkers such as circular RNAs (circRNAs) that facilitate thediagnosis and treatment of breast cancer are required to assistthe goal of reducing mortality of breast cancer. In this study, weassessed the expression of four circRNAs in breast cancer.Materials and Methods: Tumor tissues and adjacent normaltissues were obtained from ۳۹ patients with sporadic breastcancer. Divergent primers were designed to amplify the targettranscripts of circCSPP۱ (hsa_circ_۰۰۰۱۸۰۶), circNRIP۱(hsa_circ_۰۰۰۴۷۷۱), circSMAD۲ (hsa_circ_۰۰۰۰۸۴۷), andcircFOXP۱ (has_circ_۰۰۰۸۲۳۴) by quantitative real-time PCR.Sanger sequencing was performed to verify the back-splicingjunction and the circular structure of circRNAs. The expressionlevel of circRNAs in tumor tissues compared with adjacent normaltissues and the association between the expression of circRNAsand clinicopathological characteristics were analyzed.Results: We observed significant upregulation of circCSPP۱,circNRIP۱, and circSMAD۲ while the upregulation of circ-FOXP۱ was not statistically significant. The top-upregulatedcircRNA was circNRIP۱ in our study. There was a significantlyhigher expression of circCSPP۱ in estrogen receptor (ER) negativecompared to the ER-positive, progesterone receptor (PR)negative compared to the PR-positive, and human epidermalgrowth factor receptor ۲ (HER۲) negative compared to theHER۲-positive subgroups. A significantly higher expression ofcircNRIP۱ in the ER-negative subgroup was observed, as well.Conclusion: Our study revealed the upregulation of circCSPP۱,circNRIP۱, and circSMAD۲ in breast cancer tissue. These circRNAscan be potential biomarkers for breast cancer. Furtherstudies to determine their level in serum samples of patientswith breast cancer and their evaluation as a diagnostic or predictivebiomarker are required.