Dataset Information

Hsa_Circ_0066351 Acts as a Prognostic and Immunotherapeutic Biomarker in Colorectal Cancer.

ABSTRACT: Circular RNA (circRNA), a novel class of non-coding RNA, has been reported in various diseases, especially in tumors. However, the key signatures of circRNA-competitive endogenous RNA (ceRNA) network are largely unclear in colorectal cancer (CRC). We first characterized circRNAs profile by using circRNA-seq analysis from real-word dataset. The expression level of hsa_circ_0066351 in CRC tissues and cell lines was detected by quantitative real-time PCR. Then, cell proliferation assay was used to confirm the proliferation function of hsa_circ_0066351. Next, Cytoscape was used to construct circRNA-miRNA-mRNA networks. Last but not least, the landscape of hsa_circ_0066351-miRNA-mRNA in CRC had been investigated in the bulk tissue RNA-Seq level and single-cell Seq level. We proved that hsa_circ_0066351 was significantly downregulated in CRC cell lines and tissues (P < 0.001), and was negatively associated with distant metastasis (P < 0.01). Significantly, the expression of hsa_circ_0066351 was associated with better survival in patients with CRC. Function assays showed that hsa_circ_0066351 could inhibit CRC cells proliferation. In addition, a ceRNA network, including hsa_circ_0066351, two miRNAs, and ten mRNAs, was constructed. Our analyses showed that these ten mRNAs were consistently downregulated in pan-cancer and enriched in tumor suppressive function. A risk score model constructed by these ten downstream genes also indicated that they were related to the prognosis and immune response in CRC. In conclusion, we demonstrated that a novel circRNA (hsa_circ_0066351) inhibited CRC proliferation, and revealed a potential prognostic and immunotherapeutic biomarker in CRC.

SUBMITTER: Gao Y

PROVIDER: S-EPMC9667793 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Hsa_Circ_0066351 Acts as a Prognostic and Immunotherapeutic Biomarker in Colorectal Cancer.

Gao Yan Y Zhou Yulai Y Wei Le L Feng Ziyang Z Chen Yihong Y Liu Ping P Peng Yinghui Y Huang Qiaoqiao Q Gao Le L Liu Yongting Y Han Ying Y Shen Hong H Cai Changjing C Zeng Shan S

Frontiers in immunology 20220713

Circular RNA (circRNA), a novel class of non-coding RNA, has been reported in various diseases, especially in tumors. However, the key signatures of circRNA-competitive endogenous RNA (ceRNA) network are largely unclear in colorectal cancer (CRC). We first characterized circRNAs profile by using circRNA-seq analysis from real-word dataset. The expression level of hsa_circ_0066351 in CRC tissues and cell lines was detected by quantitative real-time PCR. Then, cell proliferation assay was used to ...[more]

PMID: 36405685

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Project description:Background: N6-methyladenosine (m6A) modification is a dynamic and reversible post-transcriptional RNA modification prevalent in eukaryotic cells. YT521-B homology domain family 2 (YTHDF2) has been identified as a member of m6A reader protein involving in many vital biological processes, whereas its role and functional mechanisms in cancers remain unclear. Methods: Bioinformatics analyses were performed on multiple databases including GTEx, TCGA, GEO and Cbioportal to explore the connection between YTHDF2 expression and its genomic changes including tumor mutation burden, microsatellite instability and mismatch repair in 33 different cancer types. We also investigated the association of YTHDF2 expression with prognosis, immune infiltration, tumor microenvironment, immune checkpoints and chemokines. Besides, the correlation of YTHDF2 expression with copy number variation and promoter methylation was also studied in tumors compared with normal tissues. At last, we analyzed the protein-protein interacting network and related genes of YTHDF2 to enrich its potential functional mechanism in tumor development and progression. Real-time qPCR was used to verify the expression of YTHDF2-related genes in colorectal cancer cells, and immunohistochemical staining was adopted to verify immune infiltration in tissue sections from 51 hepatocellular carcinoma patients. Results: YTHDF2 was overexpressed in a majority of tumor types and associated with their poor overall survival, progression-free interval, and disease-specific survival. The correlation of YTHDF2 expression with tumor mutation burden, microsatellite instability and mismatch repair was also detected in most of the tumor types. Moreover, YTHDF2 might participate in the immune regulation through influencing the expression of immune checkpoint genes and the infiltration of immunocytes in tumor microenvironment. Notably, we demonstrated a positive correlation between YTHDF2 expression and the infiltration of CD8+ T cells and macrophages in many tumors, and it was verified in 51 clinic hepatocellular carcinoma tissues. In addition, the involvement of YTHDF2 in "Spliceosome" and "RNA degradation" were two potential functional mechanisms underlying its influence on tumor progression. The regulation of YTHDF2 on predicted genes has been verified in CRC cells. Conclusion: YTHDF2 might be a new therapeutic target and a potential biomarker of cancer immune evasion and poor prognosis.

Project description:BackgroundB-cell receptor-associated protein 31 (BCAP31) is a widely expressed transmembrane protein primarily located in the endoplasmic reticulum (ER), including the ER-mitochondria associated membranes. Emerging evidence suggests that BCAP31 may play a role in cancer development and progression, although its specific effects across different cancer types remain incompletely understood.MethodsThe raw data on BCAP31 expression in tumor and adjacent non-tumor (paracancerous) samples were obtained from the Broad Institute Cancer Cell Line Encyclopedia (CCLE) and UCSC databases. We also examined the association between BCAP31 expression and clinicopathological factors. Using the Cox proportional hazards model, we found that high BCAP31 levels were linked to poor prognosis. To further explore BCAP31's role, we analyzed the relationship between copy number variations (CNV) and BCAP31 mRNA expression using data from The Cancer Genome Atlas (TCGA). Additionally, the association between BCAP31 expression and signature pathway scores from the MsigDB database provided insights into the tumor biology and immunological characteristics of BCAP31.We assessed the relationship between tumor immune infiltration and BCAP31 expression using the TIMER2 and ImmuCellAI databases. The ESTIMATE computational method was employed to estimate the proportion of immune cells infiltrating the tumors, as well as the stromal and immune components, based on TCGA data. To investigate drug sensitivity in relation to BCAP31 expression, we utilized GDSC2 data, which included responses to 198 medications. We explored the relationship between BCAP31 gene expression and response to immunotherapy. Additionally, the study involved culturing KYSE-150 cells under standard conditions and using siRNA-mediated knockdown of BCAP31 to assess its function. Key experiments included Western blotting (WB) to confirm BCAP31 knockdown, MTT assays for cell proliferation, colony formation assays for growth potential, Transwell assays for migration and invasion, and wound healing assays for motility. Additionally, immunohistochemistry (IHC) was performed on tumor and adjacent normal tissue samples to evaluate BCAP31 expression levels.ResultsBCAP31 was found to be significantly overexpressed in several prevalent malignancies and was associated with poor prognosis. Cox regression analysis across all cancer types revealed that higher BCAP31 levels were predominantly linked to worse overall survival (OS), disease-free interval (DFI), disease-specific survival (DSS), and progression-free interval (PFI). In most malignancies, increased BCAP31 expression was positively correlated with higher CNV. Additionally, BCAP31 expression was strongly associated with the tumor microenvironment (TME), influencing the levels of infiltrating immune cells, immune-related genes, and immune-related pathways. Drug sensitivity analysis identified six medications that showed a significant positive correlation with BCAP31 expression. Furthermore, BCAP31 expression impacted the outcomes and prognosis of cancer patients undergoing immune therapy. The functional assays demonstrated that BCAP31 knockdown in KYSE-150 cells significantly inhibited cell migration, invasion, and proliferation while enhancing colony formation ability. WB and immunohistochemistry analyses confirmed elevated BCAP31 expression in tumor tissues compared to adjacent normal tissues in esophageal cancer, lung adenocarcinoma, and gastric adenocarcinoma.ConclusionBCAP31 has the potential to serve as a biomarker for cancer immunology, particularly in relation to immune cell infiltration, and as an indicator of poor prognosis. These findings provide a new perspective that could inform the development of more targeted cancer therapy strategies.

Dataset Information

Hsa_Circ_0066351 Acts as a Prognostic and Immunotherapeutic Biomarker in Colorectal Cancer.

Publications

Hsa_Circ_0066351 Acts as a Prognostic and Immunotherapeutic Biomarker in Colorectal Cancer.

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