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types, the use of different sample collection and processing schemes, and study designs. Research on
circRNAs also faces the same issues. In summary, research on miRNA and circRNA as BC biomarkers still
faces the obstacles of inconsistency and irreproducibility. To apply miRNA and circRNA as practical
biomarkers in clinical practice, a standardized set of scientific detection methods needs to be established.
The integration of classical detection methods for multiple miRNAs and circRNAs may help improve
diagnostic capabilities.

MIRNAS AND CIRCRNAS AS PROGNOSTIC AND PREDICTIVE BIOMARKERS IN BC
Studies on circRNA and miRNA in BC tissue and serum samples have shown that the expression patterns of
these molecules are associated with tumor malignancy and poor prognosis. Analysis of circRNA and
miRNA in serum samples can provide a non-invasive method for the prognostic assessment of BC patients.

Several studies have evaluated the relationship between miRNA expression and BC survival or prognostic
prediction. High levels of miR-421, miR-128-1, and miR-128-2 were significantly associated with adverse
clinical features and cancer recurrence, and can serve as potential prognostic markers for BC . High
[50]
expression of miR-205, miR-133a, miR-21, miR-155, and miR-92b-3p were correlated with poor overall
[51]
survival in BC patients . Conversely, high expression of some miRNAs can improve the overall survival of
BC patients. For example, high expression of miR-451a and miR-367 can improve progression-free survival
and overall survival in BC patients [52,53] . In addition, miRNA expression may also predict the effects of
certain chemotherapeutic drugs and antitumor immune responses. A combination of eight serum miRNAs,
(miR-3160-5p, miR-5698, miR-4710, miR-4483, miR-575, miR-8089, miR-296-3p, and miR-4755-3p) was
established as biomarkers to predict the responsiveness to eribulin and the emergence of new distant
[54]
metastases in metastatic BC patients . Bioinformatic analysis of human BC databases revealed that high
serum and tumor miR-155 levels were correlated with favorable antitumor immune profiles and better
patient outcomes, which may be a favorable prognostic marker for BC patients . Although the above-
[55]
mentioned miRNAs as predictive markers have not yet been used in clinical applications, they provide
sufficient evidence for the use of miRNAs as prognostic markers for BC.

Similar to miRNA, there is also a relationship between circRNA expression and BC survival or prognosis.
Zhong et al. collected serum samples from 45 BC patients and 45 normal individuals for qRT-PCR analysis
[56]
and found that the expression of circRASSF2 was significantly increased in the BC group . CircRASSF2
acts as a sponge for miR-1205 and regulates the expression of HOXA1, thereby promoting BC proliferation,
migration, and invasion. BC patients with high circRASSF2 expression have lower overall survival and
progression-free survival compared to those with low circRASSF2 expression. The expression of circCDYL
is upregulated in tumor tissue and serum of BC patients, and its upregulation is associated with a higher
tumor burden, shorter survival, and poor response to clinical treatment .
[57]
MIRNAS, CIRCRNAS, AND DRUG RESISTANCE IN BC
In the treatment of malignant tumors, chemotherapy is one of the commonly used methods and has a broad
prospect for future development. However, due to the emergence of drug resistance, the therapeutic effect
of chemotherapy often fails to reach expectations. The mechanisms leading to drug resistance include
changes in the cell cycle, enhanced DNA repair, functional changes in the cell death mechanism, increased
drug efflux, and EMT. With the advancement of DNA and RNA microarray and sequencing technologies,
extensive studies have demonstrated that miRNA and circRNA play a vital role in drug resistance. A
comprehensive understanding of the role of miRNA and circRNA in the molecular mechanisms leading to
drug resistance will help to develop better strategies for cancer treatment.