Introduction : As a central catalytic component of SWI/SNF complexes, BRM has recently been documented as a significant predicator for pancreatic cancer (PC) metastasis. However, the concrete mechanisms whereby BRM promotes PC metastasis remain elusive and underexplored.

Methods : BxPC-3 and T3M4 cell lines were used to conduct gain- and loss-of function assays by transfecting corresponding vectors. The biologic functions of BRM and miR-302a-3p regarding cell mobility, migration and invasion were assessed by wound healing, transwell and pulmonary metastasis forming assays. Transcription regulation of miR-302a-3p by BRM was analyzed using chromatin immunoprecipitation (ChIP), and the underlying signaling mechanisms were explored through other molecular biologic methods. Circulating miR-302a-3p of PC patients and controls was detected by qPCR and analyzed its correlations with clinical pathological features using Chi-square test.

Results : BRM silencing reduced PC cell migration and invasion in vivo and in vitro, and these effects were associated with miR-302a-3p reduction. Overexpressed BRM increased the transcription activity of miR-302a-3p promoter and positively regulated its expression in PC cells. Up-regulated miR-302a-3p directly targeting SOCS5, a negative regulator of STAT3 signaling, to boost STAT3 phosphorylation and induce transcription of STAT3 target genes. Furthermore, miR-302a-3p was elevated in PC patient plasma and significantly associated with worse clinical pathological features.

Conclusions : Our study showed that transcriptional regulation of miR-302a-3p by BRM potentiates PC metastasis through epigenetically modulating SOCS5 expression. These data may offer accessibility to early detection of PC and provide potential therapeutic avenues to prevent deaths.