Circular RNA circ_0000372 contributes to the proliferation, migration and invasion of colorectal cancer by elevating IL6 expression via sponging miR-495.

Circular RNAs are thought to play a vital function in the progression of various cancers, including colorectal cancer (CRC). However, the biological function and mechanism of circ_0000372 in CRC are still not clear. The expression of circ_0000372 and microRNA (miR)-495 was examined by quantitative real-time PCR. Cell proliferation was evaluated using cell counting kit 8 and colony formation assays. Further, cell migration and invasion were assessed using transwell assay. Additionally, western blot analysis was used to detect the expression of proteins associated with proliferation, metastasis, Janus kinase 2 (JAK2)/signal transducers and activators of transcription (STAT3) signaling pathway and interleukin 6 (IL6). Dual-luciferase reporter assay and RNA immunoprecipitation assay were employed to verify the interaction between miR-495 and circ_0000372 or IL6. Furthermore, the effect of circ_0000372 on CRC tumor growth in vivo was explored using the mice xenograft models. Circ_0000372 was markedly upregulated in CRC, and its high expression was associated with the poor prognosis of CRC patients. Silenced circ_0000372 was able to suppress CRC cell proliferation, migration and invasion in vitro and CRC tumor growth in vivo. Bioinformatics prediction and experimental verification proposed that circ_0000372 could sponge miR-495, and miR-495 could target IL6. Besides, the JAK2/STAT3 signaling pathway activation could be regulated by circ_0000372, miR-495 and IL6. Rescue assay results confirmed that the inhibition effect of circ_0000372 knockdown on the proliferation and metastasis of CRC could be reversed by miR-495 inhibitor or IL6 overexpression. In short, we concluded that circ_0000372 promoted CRC progression by regulating the miR-495/IL6 axis, suggesting that circ_0000372 could be used as a new prognostic biomarker and therapeutic target for CRC.

Liu X ，Qin Y ，Tang X ，Wang Y ，Bian C ，Zhong J ... -  《-》

EIF4A3-induced circ_0084615 contributes to the progression of colorectal cancer via miR-599/ONECUT2 pathway.

Colorectal cancer (CRC) is a common malignant tumor. Circular RNAs (circRNAs) have been reported to take part in the progression of CRC. However, the functions of circ_0084615 in CRC development are still undefined. In this study, we aimed to explore the functions and underlying mechanisms of circ_0084615 in CRC. qRT-PCR, western blot assay and IHC assay were utilized for the levels of circ_0084615, miR-599, ONECUT2 or EIF4A3. 5-ethynyl-2'-deoxyuridine (EdU) assay and colony formation assay were conducted for cell proliferation ability. Wound-healing assay and transwell assay were applied to evaluate cell migration and invasion. Tube formation assay was used to analyze angiogenesis ability. RNA immunoprecipitation (RIP) assay, RNA pull down assay and dual-luciferase reporter assay were used to analyze the relationships of circ_0084615, miR-599, ONECUT2 and EIF4A3. Murine xenograft model assay was employed for the role of circ_0084615 in vivo. Circ_0084615 was elevated in CRC tissues and was linked to TNM stages, lymph node metastasis, differentiation and overall survival rate. Circ_0084615 knockdown inhibited CRC cell proliferation, migration, invasion and angiogenesis in vitro and hampered tumorigenesis in vivo. Circ_0084615 sponged miR-599 and miR-599 inhibition reversed circ_0084615 knockdown-mediated effects on CRC cell growth, motility and angiogenesis. ONECUT2 was identified as the target gene of miR-599. ONECUT2 overexpression recovered the effects of miR-599 on CRC malignant behaviors. Additionally, EIF4A3 induced circ_0084615 expression. EIF4A3-induced circ_0084615 played an oncogenic role in CRC development via miR-599/ONECUT2 axis.

Jiang Z ，Tai Q ，Xie X ，Hou Z ，Liu W ，Yu Z ，Liang Z ，Chen S ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

Circular RNA circ_0007142 regulates cell proliferation, apoptosis, migration and invasion via miR-455-5p/SGK1 axis in colorectal cancer.

Colorectal cancer (CRC) is a frequently diagnosed cancer worldwide. Accumulating researches suggested that circular RNA 0007142 (circ_0007142) contributed to the progression and initiation of CRC. However, the molecular mechanism of circ_0007142 in CRC needs further research. Levels of circ_0007142, microRNA-455-5p (miR-455-5p), and serum- and glucocorticoid-induced protein kinase 1 (SGK1) were identified by quantitative real-time PCR. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide assay. Flow cytometry assay was used to detect cell apoptosis in SW480 and HCT116 cells. The relative proteins expression was detected by western blot. Cell migration and invasion were evaluated using transwell assay. Moreover, dual-luciferase reporter and RNA immunoprecipitation assays were conducted to determine the relationship between miR-455-5p and circ_0007142 or SGK1. Finally, xenograft tumor model was established to confirm the effect of circ_0007142 on CRC progression in vivo. Circ_0007142 and SGK1 levels were clearly increased, while miR-455-5p level was reduced in CRC tissues and cell lines. Circ_0007142 silencing promoted cell apoptosis and inhibited cell proliferation, migration and invasion, while these effects of circ_0007142 were partially abolished by miR-455-5p inhibitor in CRC cells. Circ_0007142 could sponge miR-455-5p to regulate SGK1 expression. Moreover, the effects of miR-455-5p on cell proliferation, apoptosis, migration and invasion could be partially reversed by SGK1 overexpression. Besides, circ_0007142 knockdown also suppressed the progression of CRC in vivo. Collectively, Circ_0007142/miR-455-5p/SGK1 axis regulated cell proliferation, apoptosis, migration and invasion of CRC cells, providing a probable therapy target for CRC.

Wen T ，Wu H ，Zhang L ，Li K ，Xiao X ，Zhang L ，Zhang Y ... -  《-》

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

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.

Bai L ，Gao Z ，Jiang A ，Ren S ，Wang B ... -  《-》

Circ_0000395 promotes cell growth, metastasis and oxaliplatin resistance by regulating miR-153-5p/MYO6 in colorectal cancer.

Circular RNAs (circRNAs) are involved in the regulation of colorectal cancer (CRC) progression and chemoresistence. Here, we attempted to reveal the function and mechanism of circ_0000395 in CRC chemoresistence. The expression levels of circ_0000395, microRNA (miR)-153-5p, and myosin VI (MYO6) were determined by quantitative real-time PCR. Cell growth, metastasis and oxaliplatin resistance were evaluated via EdU assay, colony formation assay, flow cytometry, transwell assay, and cell counting kit 8 assay. Xenograft tumor model was adopted to evaluate the role of circ_0000395 on CRC tumor growth and oxaliplatin sensitivity. Protein expression of drug-resistance markers and MYO6 was analyzed by western blot. The target relationship between miR-153-5p and circ_0000395 or MYO6 was validated via dual-luciferase reporter assay and RIP assay. Circ_0000395 expression was enhanced in CRC tissues and cells. Silencing of circ_0000395 repressed CRC cell proliferation, migration and invasion, while promoted apoptosis and oxaliplatin sensitivity. Besides, circ_0000395 knockdown also reduced CRC tumor growth and enhanced the sensitivity of tumor to oxaliplatin. Additionally, circ_0000395 acted as a sponge for miR-153-5p, and miR-153-5p targeted MYO6. Functional experiments suggested that miR-153-5p inhibitor or MYO6 overexpression could reverse the suppressive effect of circ_0000395 knockdown on CRC cell growth, metastasis and oxaliplatin resistance. Circ_0000395 promoted CRC cell growth, metastasis and oxaliplatin resistance via the miR-153-5p/MYO6 axis, which might provide new insights into the treatment of CRC.

Xiao L ，Zhu Y ，Xu H ，Lin L ，Li M ，Zhou Y ... -  《-》