Novel RNA N6-methyladenosine regulator related signature for predicting clinical and immunological characteristics in breast cancer.

BACKGROUND: Epigenetic mechanismshave been reported to involve in shaping tumor immune microenvironment (TME). However, the role of RNA N6-methyladenosine (m6A) modification in breast cancerhas not been fully explored. METHODS: Based on m6A modification and TME infiltration characteristics of 2249 breast cancer patients, we comprehensively correlated m6A modification with immune landscapeby screeningcandidate genes, function analysis and constructing m6Asignatures. Principal component analysis was used to establish the m6Ascore. Both LASSO and Cox regression analyses were used to evaluate its prognostic value.Functional assays and immunohistochemistry were used to evaluate the expression of m6A regulators and immune cell infiltration. RESULTS: Based on the dysregulated expression of m6A, three distinct clusters were identified that displayed diverse types of tumour-associated TME cell infiltration in breast cancer.Gene signatures, stromal activity, and clinical prognosis were assessed by the m6Ascore. m6Ascore could function as a biomarker for predicting the therapeutic response to targeted therapy and immunotherapy.The dysregulated expression of m6Aregulators mediated the immune cell infiltration in the TME. CONCLUSION: Basedonthestudy,weidentified the signature and potential mechanism of m6AmodificationsthatmodifyTME cell infiltration. Thus, targeting m6A regulators may provide a promisingmethodoftreatingBRCA.

MicroRNA-195-3p inhibits cyclin dependent kinase 1 to induce radiosensitivity in nasopharyngeal carcinoma.

MicroRNAs (miRNAs) are revealed to participate in the progression of multiple malignancies, including nasopharyngeal carcinoma (NPC). This work is intended to decipher the function of microRNA-195-3p (miR-195-3p) in regulating the radiosensitivity of NPC cells and its mechanism. MiR-195-3p and cyclin-dependent kinase 1 (CDK1) expressions were detected in NPC tissues and cells using qRT-PCR and Western blot, respectively. Moreover, radiation-resistant cell lines were induced by continuous irradiation with different doses. Furthermore, the CCK-8 experiment, colony formation assay and flow cytometry were utilized to examine the growth, apoptosis and cell cycle of radioresistant cells. Bioinformatics prediction and dual-luciferase reporter gene assay were applied to prove the targeting relationship between miR-195-3p and CDK1 mRNA 3'UTR. The data showed that miR-195-3p was remarkably down-modulated in NPC tissues and was associated with increased tumor grade, lymph node metastasis and clinical stage of the patients. MiR-195-3p expression was significantly down-modulated in radiation-resistant NPC tissues and NPC cell lines relative to radiation-sensitive NPC tissues and human nasopharyngeal epithelial cells, while CDK1 expression was notably up-modulated. MiR-195-3p overexpression inhibited the growth of NPC cells, decreased radioresistance, promoted apoptosis, and impeded the cell cycle progression. CDK1 was a target gene of miR-195-3p, and CDK1 overexpression counteracted the effects of miR-195-3p on NPC cell growth, apoptosis, cell cycle progression and radiosensitivity. In summary, miR-195-3p improves the radiosensitivity of NPC cells by targeting and regulating CDK1.