CircFNDC3B sequestrates miR‐937‐5p to derepress TIMP3 and inhibit colorectal cancer progression

Abstract

Circular RNA (circRNA) are single‐stranded RNA with covalently closed 3′ and 5′ ends, with many recognized to be involved in human diseases as gene regulators, typically by interacting with other RNA. CircFNDC3B is a circRNA formed by back‐splicing of exons 5 and 6 of the FNDC3B gene. CircFNDC3B was recently implicated in renal carcinoma, gastric and bladder cancer. However, the expression levels of circFNDC3B and its role in colorectal cancer (CRC) remain unclear. Expression of circFNDC3B and TIMP3 levels in CRC tissues and cell lines were found to be low, whereas microRNA (miR)‐937‐5p expression was high in CRC. MicroRNA‐937‐5p downregulated TIMP3, thereby promoting tumor cell proliferation, invasion, migration and angiogenesis. Moreover, CircFNDC3B was shown to bind to miR‐937‐5p. CircFNDC3B and circFNDC3B‐enriched exosomes inhibited tumorigenic, metastatic and angiogenic properties of CRC, and miR‐937‐5p overexpression or TIMP3 knockdown could reverse these effects. In vivo CRC tumor growth, angiogenesis and liver metastasis were suppressed by circFNDC3B overexpression, circFNDC3B‐enriched exosomes or miR‐937‐5p knockdown. In conclusion, our work reports a tumor‐suppressing role for the circFNDC3B–miR‐97‐5p–TIMP3 pathway and suggests that circFNDC3B‐enriched exosomes can inhibit angiogenesis and CRC progression.

Keywords

• angiogenesis
• circFNDC3B
• colorectal cancer
• liver metastasis
• miR‐937‐5p
• TIMP3