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 0 and 5 0 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. Micro-RNA-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, circFNDC3Benriched 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.

LncRNA PART1 Promotes Proliferation and Migration, Is Associated with Cancer Stem Cells, and Alters the miRNA Landscape in Triple-Negative Breast Cancer

“…Using target prediction tools, we found that many of the protein-coding gene expression changes induced by PART1 are linked to changes in miRNAs. In addition to known effects on miR-190-3p , we report novel PART1 -mediated regulation of miR-937-5p , miR-22-5p , and miR-30b-3p in TNBC; all of which have been implicated in cancer progression in prior studies [ 71 , 72 , 73 , 74 , 75 ]. Additionally, we found that PART1 regulates miR-6870-5p ; however, in contrast to the miRNAs listed above, miR-6870-5p has not been studied previously and its function remains uncharacterized.…”

Circular RNA FNDC3B Protects Oral Squamous Cell Carcinoma Cells From Ferroptosis and Contributes to the Malignant Progression by Regulating miR-520d-5p/SLC7A11 Axis

“…It has been reported that circFNDC3B contributes to the invasion and migration by modulating CD44 and E-cadherin expression in gastric cancer cells ( 29 ). CircFNDC3B serves as a sponge of miR-937-5p to regulate TIMP3 expression and in colorectal cancer development ( 30 ). CircFNDC3B modulates renal cancer by down-regulating miR-99a expression ( 31 ).…”

Roles of circular RNAs in colorectal cancer (Review)

“…circ-ERBB2 interacting protein (ERBIN), which derives from exons 2 to 4 of the ERBIN gene, promotes angiogenesis, proliferation, invasion and migration of CRC cells by targeting miR-125a-5p and miR-138-5p; this sponging effect increases eIF4E-binding protein 1 expression, which then increases hypoxia inducible factor-1α (HIF-1α) translation and activates the HIF-1α signaling pathway ( 80 ). Zeng et al ( 81 ) revealed significantly decreased expression levels of circ-fibronectin type III domain containing 3B (FNDC3B) in CRC tissues, cell lines and exosomes. Functional experiments indicated that overexpression of circFNDC3B suppressed CRC angiogenesis, which could be reversed by overexpression of miR-937-5p ( 81 ).…”

“…Zeng et al ( 81 ) revealed significantly decreased expression levels of circ-fibronectin type III domain containing 3B (FNDC3B) in CRC tissues, cell lines and exosomes. Functional experiments indicated that overexpression of circFNDC3B suppressed CRC angiogenesis, which could be reversed by overexpression of miR-937-5p ( 81 ). Furthermore, it was demonstrated that tumor growth, angiogenesis and liver metastasis were suppressed by overexpression of circFNDC3B or circFNDC3B-exosome treatment ( 81 ).…”

“…Functional experiments indicated that overexpression of circFNDC3B suppressed CRC angiogenesis, which could be reversed by overexpression of miR-937-5p ( 81 ). Furthermore, it was demonstrated that tumor growth, angiogenesis and liver metastasis were suppressed by overexpression of circFNDC3B or circFNDC3B-exosome treatment ( 81 ).…”