N6-Methyladenosine (m6A) Reader LRPPRC-Mediated CXCL11 Induces Cell Inflammation to Drive Breast Cancer Cell Malignancy.

Abstract

Breast cancer (BC) is among the most prevalent malignant cancers in women. We examined the function and regulatory mechanism of the N6-methyladenosine (m6A) modification reader leucine-rich pentatricopeptide repeat containing (LRPPRC) in BC inflammation and progression. LRPPRC and C-X-C motif chemokine ligand 11 (CXCL11) levels were measured by quantitative real-time polymerase chain reaction. The regulatory mechanisms of LRPPRC and CXCL11 were determined by RNA binding protein immunoprecipitation, methylated RNA immunoprecipitation, and mRNA stability assays. Moreover, the function of LRPPRC and CXCL11 in BC cells was explored by cell counting kit-8, wound healing, and Transwell assays. Enzyme-linked immunosorbent assay was used to measure proinflammatory cytokine [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β) levels. LRPPRC was expressed at considerably higher levels in BC samples compared with normal tissue samples, and its overexpression predicted a poor prognosis. Reduced LRPPRC decreased BC cell viability, migration, and invasion, whereas overexpression promoted a malignant phenotype. LRPPRC exerted its stimulative effect through CXCL11 m6A modification. CXCL11 upregulation suppressed the antitumor silencing effect of LRPPRC on BC cells. CXCL11 upregulation enhanced the secretion of inflammatory factors by BC cells. LRPPRC aggravates BC inflammation and malignancy by increasing the m6A modification of CXCL11. These findings offer a potential target for BC therapy.