Circular noncoding RNA circ_0007334 sequestrates miR-577 to derepress KLF12 and accelerate colorectal cancer progression

Abstract

Colorectal cancer (CRC) is a prevalent malignant tumor with a poor prognosis. Circular RNA (circRNA) circ_0007334 is related to cell proliferation in CRC. This study is designed to explore the role and mechanism of circ_0007334 in CRC progression. Circ_0007334, microRNA-577 (miR-577) and kruppel-like factor 12 (KLF12) levels were measured by real-time quantitative PCR (RT-qPCR). Exosomes were detected by a transmission electron microscope and nanoparticle tracking analysis (NTA). CD63, TSG101, matrix metallopeptidase-2 (MMP-2), MMP-9, VEGFA and KLF12 protein levels were examined by western blot assay. The binding relationship between miR-577 and circ_0007334 or KLF12 was predicted by circRNA interactome or Starbase and verified by a dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Cell viability, colony number, migration, invasion and angiogenesis were detected by cell counting kit-8 (CCK-8), colony formation, wound healing, transwell and tube formation assays. The biological role of circ_0007334 was examined by the xenograft tumor model in vivo. Circ_0007334 and KLF12 were increased, and miR-577 was decreased in CRC tissues and cells. Also, circ_0007334 expression was upregulated in CRC cell-derived exosomes. Circ_0007334 deficiency repressed cell viability, colony formation, migration, invasion, and angiogenesis in CRC cells. Mechanically, circ_0007334 could regulate KLF12 expression by sponging miR-577. Circ_0007334 downregulation or exosomal circ_0007334 silencing blocked CRC tumor growth in vivo. These results presented that circ_0007334 deficiency exerts a tumor-suppressor by the miR-577/KLF12 axis in CRC, and indicated that exosomal circ_0007334 could hinder CRC tumor growth and angiogenesis in vivo. Our findings provided a novel therapeutic strategy for CRC. Anti-Cancer Drugs 33: e409-e422

HPV16-LINC00393 Integration Alters Local 3D Genome Architecture in Cervical Cancer Cells

“…In some cases, KLF12 was overexpressed and served as a tumor suppressor, for example, in bladder cancer ( Tang et al., 2021 ) and lung cancer ( Godin-Heymann et al., 2016 ). In other cases, KLF12 expression was correlated positively with disease severity such as in colorectal cancer ( Bai et al., 2021 ), lung cancer ( Mao et al., 2020 ), ovarian cancer ( Mak et al., 2017 ), and endometrial cancer ( Ding et al., 2019 ), indicating its tumor-promoting effect. In the present study, both the expressions of KLF12 in SiHa cells and tumor tissues based on the HPA database were significantly down-regulated compared with those in normal control cells or clinical samples.…”

Hsa_circ_0003602 Contributes to the Progression of Colorectal Cancer by Mediating the miR-149-5p/SLC38A1 Axis

“…22 And circ_0007334 deficiency restrained CRC cell growth, motility and angiogenesis via regulation of the miR-577/KLF12 axis. 23 However, the study about the function of circ_0003602 in CRC etiology is still restricted and requires further investigation. Previous research has reported that circ_0003602 was upregulated in acute myeloid leukemia.…”

Up-regulated Circular RNAs in Colorectal Cancer: New Entities for Therapy and Tools for Identification of Therapeutic Targets

“…Circ 0007334 (Figure 7) was increased in CRC tissues and in CRC-derived exosomes (192). Knockdown of 0007334 impaired viability, colony formation, migration, invasion, angiogenesis, and tumor growth of CRC cells in vivo in immuno-deficient mice (193). Circ 0007334 sponged miR-577 resulting in up-regulation of KLF12 (193).…”

“…Knockdown of 0007334 impaired viability, colony formation, migration, invasion, angiogenesis, and tumor growth of CRC cells in vivo in immuno-deficient mice (193). Circ 0007334 sponged miR-577 resulting in up-regulation of KLF12 (193). The latter is part of the Krüppel-like factor family comprising 17 members with involvement in cell differentiation, proliferation, and apoptosis.…”