 using the GEPIA database. We found that VEGFA patients had shorter RFS, and patients with high level MECP2 and ITCH had shorter OS (Figures 14 and 15, P<0.05). We then verified the correlation between has_circ_0084927, miR-106b-5p and the three hub genes by PCR, and found that only VEGFA showed significant correlation with has_circ_0084927 and miR-106b-5p in LOVO cell lines ( Figure 16).

GSEA
To further determine the possible pathways and mechanisms of these three hub genes in the COAD process, we used the TCGA database for GSEA analysis. The results showed that ITCH, MECP2 and VEGFA were mainly enriched in cell cycle, apoptosis, adherens junction, Wnt pathway, mismatch repair, P53 pathway, colorectal cancer, etc. Therefore, the circular RNA may regulate cell apoptosis and cell cycle through the ceRNA network, thereby affecting tumor progression (see Supplementary Tables 3-8).

Discussion
CircRNA is involved in the proliferation, invasion, metastasis, and apoptosis of COAD cells. Zhang et al 19 using RNAseq technology found that the overall circRNA was significantly less expressive in colorectal cancer tissue and cell lines. Compared to paracancer tissues, 125 circRNA expressions in colorectal cancer tissue were reduced, and 76 circRNA expressions were increased. 19 For example, hsa_circRNA_103809 is low expressed in colorectal cancer tissue and associated with distant metastasis. 19,20 Hsa_circ_0084927 is differentially expressed in clear cell renal cell carcinoma, 21 and it is also significantly up-regulated in lung cancer-related malignant pleural effusion and may be involved in the PI3K-Akt signaling pathway. 22 Hsa_circ_0084927 promotes the progression of CC by up-regulating TPD52 via sponge adsorption of miR-634, which provides new evidence for its use as a promising therapeutic target. 23 The significantly high expression in these tumors suggests that they may have potential cancer-promoting possibilities, which are worthy of further study. Up to now, there is very little research on hsa_circ_0084927, and more importantly, the function and mechanism of hsa_circ_0084927 have not been fully studied, and its role in tumor is unclear. Therefore, the study of hsa_circ_0084927 in COAD is of great significance. Based on sequencing data and preliminary experimental verification, our study suggested that hsa_circ_0084927 was significantly overexpressed in COAD tissue and cell lines, affecting biological behavior and prognosis, and plasma hsa_circ_0084927 can serve as a potential noninvasive biomarker in COAD.
One of the mechanisms of CircRNA is that it competitively binds with miRNA to regulate target genes. Reconfirmed by the miRCancer database, hsa-miR-106b-5p is reduced in colorectal cancer cells and can regulate downstream pathways to promote cancer development; 24 Studies have shown that hsa-miR-106b-5p is differently expressed in liver and breast cancer, but its function and mechanism have not been thoroughly clarified. 25,26 Compared with stage I-II, miR-106b is significantly down-regulated in colorectal cancer tissues at stage III-IV, inhibiting the migration and invasion of COAD cells; 27 in addition, miR-106b-5p can also inhibit the metastasis of endometrial and breast cancer; 28,29 In the Indonesian population, it can be used as a liquid biomarker for prostate cancer; 30 In the OncomiR database, we found that its expression in colon tissue is higher than that in cancer tissue, but it is of no value in terms of stage and prognosis.  Pathway enrichment analysis showed that the 134 genes were closely related to the Wnt signaling pathway, cell cycle, and colon cancer pathways. The Wnt signaling pathway plays an important role in the occurrence and development of COAD. The HPA database and immunohistochemistry showed that the expression of these 10 genes in COAD was higher than that in adjacent tissues. In this way, we confirmed our above analysis from the protein expression level, laying the foundation for the diagnosis and prognostic research of these 10 hub genes. Analysis of the Gepia database shows that VEGFA, MECP2 and ITCH are related to the prognosis of COAD patients. At the same time, we detected the expression of VEGFA, MECP2, ITCH and miR-106-5p in the three COAD cell lines, and initially verified the rationality

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of the circRNA-miRNA-mRNA regulatory network. VEGFA can promote tumor invasiveness by inducing epithelialmesenchymal transition. 31 There is a well-recognized association between high baseline circulating VEGFA levels and poor prognosis for different types of cancer. 32,33 Research shows that ITCH promotes tumor progression in hepatocellular carcinoma, breast cancer, pancreatic cancer and chronic lymphocytic leukemia. [34][35][36] The previous study indicates that the inhibition of MECP2 function in DLD1 cells leads to a decrease in cell growth, which indicates that MECP2 may be a potential target for the treatment of colorectal cancer, however, its function is far from clear. 37 The 3 hub genes we extracted were mainly rich in cell cycle, apoptosis, adherens junction, Wnt pathway, mismatch repair, the P53 pathway, colorectal cancer, and other pathways. Cell cycle and apoptosis pathways have been widely reported to have an inestimable effect on tumor occurrence, progression, and prognosis. 38 P53 pathway is abnormal in many tumors and is an important regulator of cell cycle and cell metabolism. Wnt is a critical pathway for regulating EMT.
The cancer-promoting function of hsa_circ_0084927 and its potential value as a therapeutic target can be further confirmed in future in vitro and in vivo studies and clinical trials. For example, directly interfering hsa_-circ_0084927 with drugs or designing siRNA delivery to the tumor site to interfere with the expression and function of oncogenic circRNA; using organic or inorganic materials to affect the function of circRNA. Circular RNA, as a ceRNA, is expected to replace anti-nucleotide chemical drugs and regulate the level of miRNA, in order to regulate the upstream and downstream gene networks, and have an impact on human physiology and disease. In Figure 16 Correlation analysis showed that has_circ_0084927 expression was negatively correlated with miR-106b-5p (A) and positively correlated with VEGFA (B) expression in LOVO cell lines. The expression of miR-106b-5p was negatively correlated with VEGFA expression (C). In HCT116, has_circ_0084927 expression was negatively correlated with miR-106b-5p (D), but not with VEGFA (E) expression. The expression of miR-106b-5p was negatively correlated with VEGFA (F). recent years, many studies have reported the application of circular RNAs as potential therapeutic targets. For example, Xu Bin et al 39 designed and synthesized si-ciRS-7 specific for ciRS-7, and successfully prepared PBAE/si-ciRS-7 nanometers Complex. Their study confirms that drug development of PBAE/si-ciRS-7 nanocomplexes targeting ciRS-7 may be a promising therapeutic strategy for renal cell carcinoma. Wang et al demonstrated that targeting ciRS-122 by systemic injection of exosome-delivered siRNA in an oxaliplatin-resistant mouse model of CRC sensitized CRC to oxaliplatin, suggesting a new potential method can reverse oxaliplatin resistance in CRC. 40 Down-regulated circRNAs have been shown to negatively regulate CRC growth and metastasis. Inducing the expression of these tumor suppressor circRNAs by physicochemical factors in CRC cells or tissues may have significant antitumor effects. 41 This study preliminarily verified that hsa_circ_0084927 could play a tumor-promoting role in COAD, and proposed that it could be used as a non-invasive detection marker for prognostic assessment in plasma and effectively established the hsa_circ_0084927/miR-106b-5p/VEGFA network. In addition, it is also found that VEGFA, MECP2 and ITCH in the network may affect the prognosis of COAD patients by regulating the cell cycle and other ways. However, the specific mechanisms by which hsa_circ_0084927 and ceRNA networks regulate the development of COAD deserve further study.

Data Sharing Statement
The original data supporting the article is included in the article/Supplementary Materials.

Ethics Approval
This study was approved by the Ethics and Human Subject Committee of Guangxi Medical University Cancer Hospital (LW2022020).In this episode, Amy shares 5 simple steps to help you get your life together…and GATLUW!
Amy starts us off by debating what is the life you are going after. She guides today's conversation with the question, “What is a life together for you actually look like?”.
Amy discusses the importance of starting the day on YOUR terms. If you aren't starting the day by living for you, you more than likely won't continue to live for yourself.
You have to be able to give yourself a life to live! Easy steps to do this include making sure you are taking care of your body and mind.
Think about the different types of people who you talk to on a daily. 
Amy wants us to commit to getting better sleep! Trying out this simple step could lead you to a new lifestyle of getting your life together!
This is my life and I both can’t believe it and am so, so grateful and happy.
Crivens has hit kitten adolescence at full speed. We now must keep the bathroom door shut at all times; he is 9