<p>Circ_0005576 Promotes Malignant Progression Through miR-874/CDK8 Axis in Colorectal Cancer</p>

Abstract

Purpose: To investigate the function of circ_0005576 in colorectal cancer (CRC) progression. Patients and Methods: Circ_0005576 expression in CRC patients was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). CRC cells were transfected using Lipofectamine 2000 reagent. CRC cell proliferation was researched by Cell Counting Kit-8 (CCK-8) assay and 5-ethynyl-2-deoxy-uridine (EdU) incorporation experiment. Cell cycle and apoptosis were determined by flow cytometry analysis. Luciferase reporter assay was used to explore the relationship between circ_0005576 and miR-874 or between miR-874 and CDK8. qRT-PCR and Western blot were used to detect circ_0005576, miR-874, and CDK8 expression. In vivo experiments were performed using nude mice. CDK8 and Ki67 expression in xenograft tumors was investigated by immunohistochemistry. Tunel assay was conducted to analyze the apoptosis of xenograft tumors. Results: Circ_0005576 expression was up-regulated in CRC, which was associated with tumor progression (P < 0.05 or P < 0.01). Circ_0005576 knockdown in CRC cells reduced proliferation, induced apoptosis, increased cells in the G1 phase, and decreased cells in the S phase (P < 0.01 or P < 0.001). Circ_0005576 promoted CDK8 expression via sponging miR-874. miR-874 knockdown and CDK8 overexpression significantly reversed the inhibitory effect of circ_0005576 knockdown on CRC cells malignant phenotype (P < 0.05 or P < 0.01). Circ_0005576 knockdown inhibited tumor growth in vivo (P < 0.01). Circ_0005576 knockdown reduced CDK8, Ki67 expression, and enhanced apoptosis in xenograft tumors. Conclusion: Circ_0005576 promoted malignant progression through the miR-874/CDK8 axis in CRC.

Hsa_circ_0005576 promotes osimertinib resistance through the miR‐512‐5p/IGF1R axis in lung adenocarcinoma cells

“…5 Two previous studies pointed out that hsa_circ_0005576 is an oncogene that can mediate the progression of colorectal cancer and cervical cancer. 12,13 At this time, there have been no other reports on F I G U R E 5 A, Heat map of the transcriptome microarray of differentially expressed genes in H1975OR cells transfected with or without sh-circ_0005576. B, Signaling pathway enrichment analysis by transcriptome microarray for differentially expressed genes of H1975OR cells transfected with or without sh-circ_0005576.…”

“…10,11 Recently, hsa_circ_0005576 has been demonstrated to promote malignant progression in colorectal cancer through the miR-874/CDK8 axis. 12 Furthermore, upregulated hsa_circ_0005576 was associated with cervical cancer progression through the miR-153/ KIF20A axis. 13 Nevertheless, the expression patterns and functions of hsa_circ_0005576 involved in EGFR-TKI resistance of LUAD are still almost unknown.…”

miR-874: An Important Regulator in Human Diseases

“…As shown in Table 1 , miR-874 is downregulated in at least 22 human malignancies, such as colorectal cancer (CRC) ( Huang et al, 2020a ; Yu et al, 2020 ; Que et al, 2017 ; Zhao and Dong, 2016 ; Han et al, 2016 ; Wang et al, 2021 ; Zhang et al, 2021c ), gastric cancer (GC) ( Huang et al, 2018 ; Sun et al, 2020 ; Yuan et al, 2020 ; Liu et al, 2017 ; Zhang et al, 2015 ; Jiang et al, 2014 ), hepatocellular carcinoma (HCC) ( Zhang et al, 2018b ; Jiang et al, 2017 ; Leong et al, 2017 ; Song et al, 2016 ), esophageal squamous cell carcinoma (ESCC) ( Yuan et al, 2018 ), pancreatic ductal adenocarcinoma (PDAC) ( Diao et al, 2018 ), non-small cell lung cancer (NSCLC) ( Bu et al, 2020 ; Yang et al, 2017 ; Ahmad et al, 2015 ; Kesanakurti et al, 2013 ; Wang et al, 2020b ), osteosarcoma (OS) ( Tang et al, 2018 ; Liu et al, 2020 ; Dong et al, 2016 ; Ghosh et al, 2017 ), epithelial ovarian cancer (EOC) ( Xia et al, 2018 ) cervical cancer (CC) ( Liao et al, 2018 ; Liu et al, 2021a ), retinoblastoma (RB) ( Zhang et al, 2018a ; Wang et al, 2020a ), prostate cancer (PCa) ( Pashaei et al, 2017 ) maxillary sinus squamous cell carcinoma (MSCC) ( Nohata et al, 2011 ), breast cancer (BC) ( Li et al, 2020 ; Zhang et al, 2017 ; Wang et al, 2014 ), triple-negative breast cancer (TNBC) ( Wu et al, 2020 ), rhabdomyosarcoma (RMS) ( Shang et al, 2019 ), papillary thyroid carcinoma (PTC) ( Ding et al, 2021 ), endometrial cancer ( Witek et al, 2021 ), cholangiocarcinoma ( Pan et al, 2021 ), glioma ( Li et al, 2021a ), myeloma (MM) ( Tian et al, 2021 ), head and neck squamous cell carcinoma (HNSCC) ( Nohata et al, 2013 ) and acute myeloid leukemia (AML) ( Zhang et al, 2021a ).…”

“…In CRC, the MCF2LAS1/miR-874-3p/FOXM1 axis ( Liao et al, 2018 ) and MCF2LAS1/miR-874-3p/CCNE1 axis ( Huang et al, 2020a ) can promote cancer cell apoptosis, inhibit cancer cell proliferation, invasion, migration and EMT process. Also, the circ_0005576/miR-874/CDK8 axis can promote the malignant progression of CRC ( Yu et al, 2020 ). In CRC cells, circ_0007142 can regulate the level of GDPD5 by sponging miR-874-3p (12).…”

Circ-RNF121 regulates tumor progression and glucose metabolism by miR-1224-5p/FOXM1 axis in colorectal cancer

“…Circular RNA (circRNA) is a noncoding RNA with high stability [ 4 ], and is generated from the exonic regions of coding gene via back-splicing [ 5 ]. Multiple researches have reported that circRNAs participate in regulating cancer development [ 6 , 7 ]. In particular, circ-ring finger protein 121 (circ-RNF121), only named as circ_100876, regulates the development of digestive system-related cancers.…”