Cancer-associated fibroblasts-derived exosomes upregulate microRNA-135b-5p to promote colorectal cancer cell growth and angiogenesis by inhibiting thioredoxin-interacting protein

Abstract

Objective: The role of exosomes in human cancers has been identified, while the effect of cancer-associated fibroblasts (CAFs)-derived exosomes (CAF-exos) transmitting microRNAs (miRNAs) on colorectal cancer (CRC) remains largely unknown. We aim to explore the impact of CAF-derived exosomal miR-135b-5p on CRC progression by targeting thioredoxin-interacting protein (TXNIP).

Methods: CRC tissues were collected to obtain CAF-exos, which were used to co-culture with LoVo and HT29 cells. The effect of miR-135b-5p and TXNIP on the in vivo growth, in vitro proliferation, apoptosis, migration, invasion and angiogenesis of CRC cells. miR-135b-5p and TXNIP expression in exosomes and CRC cells were detected and their targeting relationship was confirmed.

Results: MiR-135b-5p was upregulated whereas TXNIP was downregulated in CRC tissues and cells. The CAF-exos and CAF-exos upregulating miR-135b-5p promoted in vivo growth, in vitro proliferation, migration and invasion, and suppressed apoptosis of CRC cells, and also promoted the HUVEC angiogenesis. TXNIP was confirmed as a target of miR-135b-5p and overexpression of TXNIP could weaken the pro-CRC effect of exosomal miR-135b-5p, CONCLUSION: CAF-exos upregulate miR-135b-5p to promote CRC cell growth and angiogenesis by inhibiting TXNIP.

Keywords: Apoptosis; Cancer-associated fibroblasts-derived exosome; Colorectal cancer; MicroRNA-135b-5p; Proliferation; Thioredoxin-interacting protein.