High collagen type XI alpha 1 (COL11A1) levels are associated with tumor progression, chemoresistance, and poor patient survival in several cancer types. MicroRNAs (miRNAs) are dysregulated in multiple cancers, including epithelial ovarian carcinoma (EOC); however, the regulation of COL11A1 by miRNAs in EOC remains unclear. We examined the role of miRNAs in regulating COL11A1 expression. We identified miR-509 and miR-335 as the candidate miRNAs through an online database search. EOC cell treatment with miR-335 mimics abrogated COL11A1 expression and suppressed cell proliferation and invasion, besides increasing the sensitivity of EOC cells to cisplatin. Conversely, treatment with miR-335 inhibitors prompted cell growth/invasiveness and chemoresistance of EOC cells. miR-335 inhibited COL11A1 transcription, thus reducing the invasiveness and chemoresistance of EOC cells via the Ets-1/MMP3 and Akt/c/EBPβ/PDK1 axes, respectively. Furthermore, it did not directly regulate PDK1 but increased PDK1 ubiquitination and degradation through COL11A1 inhibition. In vivo findings highlighted significantly decreased miR-335 mRNA expressions in EOC samples. Furthermore, patients with low miR335 levels were susceptible to advanced-stage cancer, poor response to chemotherapy, and early relapse. This study highlighted the importance of miR-335 in downregulating COL11A1-mediated ovarian tumor progression, chemoresistance, and poor survival and suggested its potential application as a therapeutic target.

Dendritic cell (DC)-based cancer immunotherapy remains limited by heterogeneous immune responses and variable clinical efficacy. CD86, a key co-stimulatory molecule, is traditionally regarded as a marker of dendritic cell maturation; however, accumulating evidence suggests that CD86 expression is regulated by immune checkpoint interactions, inflammatory signaling, and tumor microenvironment-associated immune modulation. In this review, we summarize current evidence regarding the molecular mechanisms governing CD86 regulation, including MARCH1-mediated ubiquitination and CTLA-4-mediated trans-endocytosis, and discuss how suppressive cytokines, hypoxia, and metabolic stress influence dendritic cell function within the tumor microenvironment (TME). We further review the heterogeneity of CD86 regulation across dendritic cell subsets and immune contexts, as well as its potential relevance in secondary lymphoid organs and tumor-associated immune responses. In addition, we discuss current evidence regarding soluble CD86 (sCD86) and its reported associations with immune activation and dysregulated immune states in cancer. Current evidence supports that CD86 regulation is shaped by integrated co-stimulatory signaling, immune checkpoint interactions, and tumor microenvironment-associated suppression. Importantly, CD86 may function not only as a dendritic cell maturation marker but also as a dynamic immunoregulatory molecule with context-dependent implications in cancer immunity. However, substantial uncertainties remain regarding its mechanistic role, prognostic value, and therapeutic relevance across different tumor settings. Future mechanistic and translational studies are needed to clarify these unresolved issues.

Biomarkers that predict disease progression may assist in the development of better therapeutic strategies for aggressive cancers, such as ovarian cancer. This study aimed to investigate the role of collagen type IV alpha 6 (COL4A6) in cell invasiveness, tumor formation, chemoresistance, and the prognostic impact of COL4A6 expression in ovarian cancer. COL4A6 regulated discoidin domain receptor 1 (DDR1)/p-DDR1 expression through the binding of E2F transcription factor 1 (E2F) to its putative DDR1 promoter binding site, suggesting that the E2F–DDR1 axis is upregulated by COL4A6. Pharmacological inhibition of DDR1 abrogated COL4A6-dependent cell invasiveness and chemoresistance. COL4A6 regulated cell invasion via the E2F1/DDR1/focal adhesion kinase axis; in contrast, COL4A6 regulated cell sensitivity to cisplatin via the DDR1/nuclear factor-kappa B axis. DDR1-IN-1 increased cell sensitivity to cisplatin, synergized with cisplatin to suppress the invasive ability and oncogenic potential of ovarian cancer cells, and decreased tumor formation in mouse xenografts. High COL4A6 mRNA levels were associated with advanced disease stages and poor chemotherapy response. The 5-year recurrence-free and overall survival rates were significantly lower in patients with high tissue COL4A6 mRNA expression levels than in those with low expression levels. COL4A6 may promote tumor aggressiveness and chemoresistance via the E2F/DDR1 axis, and COL4A6 expression can predict clinical outcomes in patients with ovarian cancer. DDR1 should be targeted in patients with COL4A6-positive tumors.