Inhibition of breast cancer cell growth and migration through siRNA-mediated modulation of circ_0009910/miR-145-5p/MUC1 axis

Maryam Abtin; Nahid Nafisi; Asghar Hosseinzadeh; Sepideh Kadkhoda; Ramesh Omranipour; Leyla Sahebi; Masoumeh Razipour; Soudeh Ghafouri-Fard; Abbas Shakoori

doi:10.1016/j.ncrna.2024.01.016

Inhibition of breast cancer cell growth and migration through siRNA-mediated modulation of circ_0009910/miR-145-5p/MUC1 axis

Noncoding RNA Res. 2024 Jan 26;9(2):367-375. doi: 10.1016/j.ncrna.2024.01.016. eCollection 2024 Jun.

Authors

Affiliations

¹ Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
² Surgery Department, Rasoul Akram Hospital Clinical Research Development Center (RCRDC), Iran University of Medical Sciences, Tehran, Iran.
³ Breast Disease Research Center (BDRC), Tehran University of Medical Sciences, Tehran, Iran.
⁴ Department of Surgical Oncology, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁵ Maternal, Fetal and Neonatal Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁶ Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁷ Department of Medical Genetics, Cancer Institute of Iran, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Dr. Qarib St., Keshavarz Blvd, Tehran, Iran.

Abstract

Circular RNAs (circRNAs) characterize a novel kind of regulatory RNAs distinguished by great evolutionary conservation and constancy. Although their exact role in malignancies is not fully understood, they mainly work through specific axes. Circular RNA/miRNA/mRNA axes affect the pathogenesis of human cancers including breast cancer. We assessed the expression and function of circ_0009910/miR-145-5p/MUC1 axis in Breast Cancer tissues and MCF-7 cells. Expression levels of circ_0009910 and MUC1 were notably increased in breast cancer tissues compared with control tissues, parallel with the down-regulation of miR-145-5p. Clinicopathological analysis indicated that up-regulation of circ_0009910 in breast tumors is related to invasion of the tumor to lymph node (P value = 0.011). Also, the downregulation of miR-145-5p was significantly correlated with tumor invasion to lymph nodes (P value = 0.04) and HER2-negative tumors (P value = 0.037). Finally, overexpression of MUC1 was correlated with age under 45 years (P value = 0.002). More importantly, circ_0009910-siRNA decreased the proliferation and migration ability of breast cancer cells, enhanced expression of miR-145-5p, and decreased levels of MUC1. Taken together, the circ_0009910/miR-145-5p/MUC1 axis has been demonstrated to affect the pathogenesis of breast cancer and might provide a target for breast cancer treatment.

Keywords: Breast cancer; Circ_0009910; MUC1; miR-145-5p.