BRM transcriptionally regulates miR-302a-3p to target SOCS5/STAT3 signaling axis to potentiate pancreatic cancer metastasis. (1st May 2019)

• Record Type: Journal Article
• Authors: Zhang, Zhengkui; Li, Jisong; Guo, Huahu; Wang, Feng; Ma, Ling; Du, Chong; Wang, Yazhou; Wang, Qi; Kornmann, Marko; Tian, Xiaodong; Yang, Yinmo
• Is Part Of: Cancer letters. Volume 449(2019)
• Page Start: 215
• Page End: 225
• Publication Date: 2019-05-01
• Subjects: BRM -- miR-302a-3p -- SOCS5 -- STAT3 -- Pancreatic cancer -- Metastasis; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2019.02.031
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Brahma (BRM) has recently been documented as a significant predictor of pancreatic cancer (PC) metastasis. This study aimed to further elucidate molecular mechanism by which BRM promotes PC metastasis. We found that silencing BRM reduced PC cell migration and invasion both in vivo and in vitro, accompanied by reduced level of miR-302a-3p. BRM positively regulated the transcription of miR-302a-3p, which acted as a metastasis-promoting miRNA in PC cells. miR-302a-3p directly targeted SOCS5 to boost STAT3 phosphorylation and induce the transcription of STAT3 target genes. Furthermore, miR-302a-3p level was higher in tissue and plasma samples derived from PC patients, and was significantly associated with worse clinical pathological features. In xenograft models, inhibiting miR-302a-3p was synergistically lethal in BRM-silenced PC cells. In conclusion, our results suggest that transcriptional regulation of miR-302a-3p by BRM potentiates PC metastasis by epigenetically suppressing SOCS5 expression and activating STAT3 signaling. These new findings provide potential therapeutic avenues for preventing PC-associated death. Highlights: BRM positively regulated the transcription of miR-302a-3p. miR-302a-3p directly targeted SOCS5. miR-302a-3p induced the transcription of STAT3 target genes. Inhibiting miR-302a-3p was synergistically lethal in BRM-silenced PC cells. miR-302a-3p level was higher in tissue and plasma samples derived from PC patients.