Breast cancer (BC) remains the most prevalent tumor and the leading cause of death among women worldwide, despite the advancements in diagnosis and new treatments. A significant challenge in BC treatment is the acquired or de novo resistance of tumors to systemic therapy. To overcome this obstacle, personalized treatment is needed, with a focus on finding biomarkers capable of predicting the response to therapy. MicroRNAs (miRNAs) have emerged as potential markers due to their diverse clinical applications.


AIM
To examine the potential prognostic significance of miR-125b-2, -155, -221, and -320a expression in the tumor cells of individuals with hormone-dependent BC before undergoing neoadjuvant hormonal therapy.


MATERIALS AND METHODS
The study is based on a retrospective analysis of the treatment outcome of 56 patients with stage II-III locally disseminated hormone-dependent BC. The real-time quantitative reverse transcription polymerase chain reaction was performed on the biopsy material to assess the expression of miR-125b-2, -155, and -221 before neoadjuvant hormonal therapy with aromatase inhibi- tor letrozole to predict clinical response.


RESULTS
Most HER2/neu+ BC patients had low levels of miR-155 and miR-221 expression in tumor biopsy specimens. Tumors that responded well to letrozole exhibited lower levels of miR-125b-2 and miR-221 compared to non-responsive tumors.


CONCLUSIONS
miR-125b-2, -155, and -221 expres- sion can predict resistance to the letrozole treatment of BC.

ASSOCIATION OF miRNA EXPRESSION PATTERN WITH OUTCOME OF LETROZOLE THERAPY IN BREAST CANCER PATIENTS.

Abstract MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play important roles in cancer development and progression. MiR-125b-5p is a miRNA that has been reported to have diverse and context-dependent effects on different cancer types and subtypes. In this study, we aimed to investigate the expression and function of miR-125b-5p in MCF-7 breast cancer cells and to explore the potential of using chitosan nanoparticles for miR-125b-5p delivery. We found that miR-125b-5p was downregulated in MCF-7 cells compared to normal mammary epithelial cells, and that its overexpression reduced the viability of MCF-7 cells by targeting Raf-1 and BMPR1b genes, which are involved in cell survival and proliferation. We also synthesized and characterized chitosan/miR-125b nanoparticles (CNPs) and evaluated their in vitro release profile and cellular uptake. We showed that CNPs enhanced the delivery and efficiency of miR-125b-5p, resulting in a more potent inhibition of Raf-1 and BMPR1b gene expression and a greater reduction of cell viability. Our results suggest that miR-125b-5p and CNPs have potential anti-tumor effects on human breast cancer cells by suppressing Raf-1 and BMPR1b gene expression. Our study provides a new insight into the role and mechanism of miR-125b-5p and its target genes in breast cancer, and demonstrates the feasibility and efficacy of using chitosan nanoparticles for miR-125b-5p delivery. 

Synthesis and evaluation of chitosan/miR-125b nanoparticles for targeting Raf-1 and BMPR1b genes in MCF-7 breast cancer cells

Summary. Hormone-dependent malignant neoplasms are the most common form of breast cancer (BC) worldwide. The high heterogeneity of clinical manifestations and response to treatment indicates the need to search for prognostic and predictive markers to predict the aggressiveness of the course of hormone-dependent BC and prescribe individualized treatment tactics. MicroRNAs are short RNA molecules that play an important role in regulating the expression of many genes. This is due to the fact that miRNAs are important modulators of growth, differentiation and metastasis of malignant neoplasms of various histogenesis, including BC. MicroRNAs can be used to predict the course of the disease and choose optimal treatment tactics, since their levels can be determined not only in tumor tissue but also in blood serum. The systematization and generalization of the results of our own research and data from the literature on the possibility of using miRNA as predictive markers of hormone-dependent BC indicates the perceptiveness of using miRNA to monitor the course of the tumor process and to determine the sensitivity of tumors to neoadjuvant hormonal therapy.

PROSPECTS OF USING microRNAs AS PREDICTIVE MARKERS OF HORMONE-DEPENDENT BREAST CANCER

BACKGROUND
Hormonal therapy is one of the main methods of comprehensive treatment of patients with locally advanced breast cancer (BC). Despite the intensive search for molecules associated with the aggressiveness of the tumor process, currently there are no reliable markers predicting response to neoadjuvant hormonal therapy (NHT).


AIM
To investigate the correlation between miR-125b-2, -155, -221, -320a expression in tumor tissue and HER2/neu status and response to tamoxifen treatment in BC patients.


MATERIALS AND METHODS
Expression levels of miR-125b-2, -155, -221, and -320a were analyzed in biopsy samples of 50 BC patients using a real-time polymerase chain reaction.


RESULTS
We found that levels of miR-125b-2, -155, -221, and -320a were 1.72, 1.65, 1.85, and 2.89 times higher in BC biopsy samples expressing estrogen/progesterone receptors and HER2/neu compared with HER2/neu-negative luminal tumors. Patients with a luminal BC showing higher levels of miR-125b-2 and miR-320a expression before therapy demonstrated better response to NHT with tamoxifen. A strong correlation was calculated for miR-221 expression and response to NHT (r = 0.61).


CONCLUSIONS
The high levels of miR-125b-2, -155, -221, and -320a in tumor tissue are associated with the HER2/neu-positive status of luminal BC subtypes. Tumor samples of patients showing the low response to NHT with tamoxifen are characterized by lower expression of miR-125b-2 and -320a. Hence, miR-125b-2 and -320a could be considered as putative predictive biomarkers associated with tamoxifen sensitivity of hormone-dependent BC.

EXPRESSION PATTERN OF miR-125b-2, -155, -221, AND -320a IS ASSOCIATED WITH RESPONSE OF BREAST CANCER PATIENTS TO TAMOXIFEN.

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EXPRESSION PATTERN OF miR-125b-2, -155, -221, AND -320a IS ASSOCIATED WITH RESPONSE OF BREAST CANCER PATIENTS TO TAMOXIFEN.

ASSOCIATION OF miRNA EXPRESSION PATTERN WITH OUTCOME OF LETROZOLE THERAPY IN BREAST CANCER PATIENTS.

PROSPECTS OF USING microRNAs AS PREDICTIVE MARKERS OF HORMONE-DEPENDENT BREAST CANCER