Citation: Lisencu, L.A.; Roman, A.; Visan, S.; Bonci, E.-A.; Pas , ca, A.; Grigorescu, E.; Mustea, E.; Cismaru, A.; Irimie, A.; Lisencu, C.; et al. The Role of miR-375-3p, miR-210-3p and Let-7e-5p in the Pathological Response of Breast Cancer Patients to Neoadjuvant Therapy. Medicina 2022, 58, 1494. https://doi.org/10.3390/ medicina58101494 Academic Editor: Maria Rosaria De Miglio Received: 9 July 2022 Accepted: 13 October 2022 Published: 20 October 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). medicina Article The Role of miR-375-3p, miR-210-3p and Let-7e-5p in the Pathological Response of Breast Cancer Patients to Neoadjuvant Therapy Lorena Alexandra Lisencu 1 , Andrei Roman 2 , Simona Visan 3 , Eduard-Alexandru Bonci 1,4 , Andrei Pas , ca 1,4 , Emilia Grigorescu 5 , Elena Mustea 5 , Andrei Cismaru 6 , Alexandru Irimie 1,4 , Cosmin Lisencu 1,4 , Loredana Balacescu 3,7, *, Ovidiu Balacescu 3,7 and Oana Tudoran 3,7, * 1 Department of Oncological Surgery and Gynecological Oncology, “Iuliu Hat , ieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania 2 Department of Radiology, The Oncology Institute “Prof. Dr. Ion Chiricut , ă”, 400015 Cluj-Napoca, Romania 3 Department of Genetics, Genomics and Experimental Pathology, The Oncology Institute “Prof. Dr. Ion Chiricut , ă”, 400015 Cluj-Napoca, Romania 4 Department of Surgical Oncology, The Oncology Institute “Prof. Dr. Ion Chiricut , ă”, 400015 Cluj-Napoca, Romania 5 Department of Pathological Anatomy, County Emergency Hospital, 400347 Cluj-Napoca, Romania 6 Research Center for Functional Genomics, Biomedicine and Translational Medicine, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400037 Cluj-Napoca, Romania 7 11th Department of Medical Oncology, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400012 Cluj-Napoca, Romania * Correspondence: lbalacescu@iocn.ro (L.B.); oana.tudoran@iocn.ro (O.T.); Tel.: +40-264590638 (O.T.) Abstract: Background and Objectives: Prediction of response to therapy remains a continuing challenge in treating breast cancer, especially for identifying molecular tissue markers that best character- ize resistant tumours. Microribonucleic acids (miRNA), known as master modulators of tumour phenotype, could be helpful candidates for predicting drug resistance. We aimed to assess the associ- ation of miR-375-3p, miR-210-3p and let-7e-5p in breast cancer tissues with pathological response to neoadjuvant therapy (NAT) and clinicopathological data. Material and methods: Sixty female pa- tients diagnosed with invasive breast cancer at The Oncology Institute “Ion Chiricut , ă”, Cluj-Napoca, Romania (IOCN) were included in this study. Before patients received any treatment, fresh breast tissue biopsies were collected through core biopsy under echographic guidance and processed for total RNA extraction and miRNA quantification. The Cancer Genome Atlas Breast Invasive Car- cinoma (TCGA-BRCA) database was used as an independent external validation cohort. Results: miR-375-3p expression was associated with more differentiated tumours, hormone receptor presence and lymphatic invasion. According to the Miller–Payne system, a higher miR-375-3p expression was calculated for patients that presented with intermediate versus (vs.) no pathological response. Higher miR-210-3p expression was associated with an improved response to NAT in both Miller–Payne and RCB evaluation systems. Several druggable mRNA targets were correlated with miR-375-3p and miR-210-3p expression, with upstream analysis using the IPA knowledge base revealing a list of possible chemical and biological targeting drugs. Regarding let-7e-5p, no significant association was noticed with any of the analysed clinicopathological data. Conclusions: Our results suggest that tumours with higher levels of miR-375-3p are more sensitive to neoadjuvant therapy compared to resistant tumours and that higher miR-210-3p expression in responsive tumours could indicate an excellent pathological response. Keywords: breast cancer; neoadjuvant therapy; pathological complete response; miR-375-3p; let-7e-5p; MiR-210-3p Medicina 2022, 58, 1494. https://doi.org/10.3390/medicina58101494 https://www.mdpi.com/journal/medicina