Circular RNA hsa_circ_0000567 can be used as a promising diagnostic biomarker for human colorectal cancer

Background

Recent studies have revealed that circular RNAs are involved in the biological process of some kinds of human cancers. However, little is known about their diagnostic values and functions in colorectal cancer (CRC).

Methods

The expression levels of hsa_circ_0000567 in 102 paired CRC tissues and adjacent noncancerous tissues, 5 CRC cell lines, and a normal colorectal epithelial cell line were detected by quantitative real‐time polymerase chain reaction (qRT‐PCR). The correlations between hsa_circ_0000567 expression levels and the clinicopathological factors of patients with CRC were analyzed. Furthermore, the loss‐of‐function assay was performed to investigate the functions of hsa_circ_0000567 in vitro. Finally, a receiver operating characteristic (ROC) curve was established to evaluate the diagnostic value of hsa_circ_0000567.

Results

Hsa_circ_0000567 expression was significantly downregulated in CRC tissues and CRC cell lines. In addition, the decreased hsa_circ_0000567 expression in CRC was negatively correlated with tumor size (P = .011), lymph metastasis (P = .003), distal metastasis (P < .0001), and tumor–node–metastasis (TNM) stage (P = .003) in CRC. Moreover, knockdown of hsa_circ_0000567 promoted CRC cells proliferation and migration in vitro. Importantly, the area under the ROC curve (AUC) was 0.8653, which indicates hsa_circ_0000567 can serve as a diagnostic biomarker.

Conclusion

Hsa_circ_0000567 may be a novel suppressor and a potential diagnosis biomarker in CRC.

     

CircRNAs as promising biomarker in diagnosis of breast cancer: An updated meta‐analysis

BackgroundCircular RNAs (circRNAs) have been identified to be involved in onset and progression of multiple malignant tumors. The present study aimed to systematically evaluate the diagnostic values of circRNAs in breast cancer.MethodsThe PubMed, Web of Science, Embase, CNKI, and Wanfang online databases were searched for the relevant studies before December 31, 2020. Statistical analysis of the diagnostic tests was performed based on STATA 16.0, Meta‐DiSc 1.4, and RevMan 5.3 software. The threshold effect and publication bias were measured by the Spearman correlation and Deeks’ funnel plot asymmetry test, respectively.ResultsTwenty‐one studies from 13 articles were included in this meta‐analysis. The pooled sensitivity and specificity were 0.77 and 0.71, respectively. The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR), and overall diagnostic odds ratio (DOR) were 2.6, 0.33, and 8, respectively. Furthermore, the area under the summary receiver operator characteristic curve was 0.80. In addition, down‐regulated circRNAs achieved a diagnostic performance higher than up‐regulated circRNAs, with area under curve (AUC) values of 0.81 and 0.74, respectively. Studies based on tissue samples presented better diagnostic accuracy than those based on plasma samples, with AUC values of 0.80 and 0.67. In addition, two circRNAs, including circ_0001073 and circTADA2A‐E5/E6, showed higher diagnostic values, with AUC value of 0.990 and 0.937, respectively. According to the results of meta‐regression, the case size (p<0.05) might be the source of the heterogeneity.ConclusionCircRNAs exhibited a high diagnostic value for breast cancer and may function as potential diagnostic biomarkers for breast cancer.     

Identification of a stool long non‐coding RNAs panel as a potential biomarker for early detection of colorectal cancer

BackgroundThe feces of colorectal cancer (CRC) patients contain tumor colonocytes, which constantly shed into the lumen area. Therefore, stool evaluation can be considered as a rapid and low‐risk way to directly determine the colon and rectum status. As long non‐coding RNAs (lncRNAs) alterations are important in cancer cells fate regulation, we aimed to assess the level of a panel of cancer‐related lncRNAs in fecal colonocytes.MethodsThe population study consisted of 150 subjects, including a training set, a validation set, and a group of 30 colon polyps. The expression levels of lncRNAs were evaluated by quantitative real‐time PCR (qRT‐PCR). The NPInetr and EnrichR tools were used to identify the interactions and functions of lncRNAs.ResultsA total of 10 significantly dysregulated lncRNAs, including CCAT1, CCAT2, H19, HOTAIR, HULC, MALAT1, PCAT1, MEG3, PTENP1, and TUSC7, were chosen for designing a predictive panel. The diagnostic performance of the panel in distinguishing CRCs from the healthy group was AUC: 0.8554 in the training set and 0.8465 in the validation set. The AUC for early CRCs (I‐II TNM stages) was 0.8554 in the training set and 0.8465 in the validation set, and for advanced CRCs (III‐IV TNM stages) were 0.9281 in the training set and 0.9236 in the validation set. The corresponding AUC for CRCs vs polyps were 0.9228 (I‐IV TNM stages), 0.9042 (I‐II TNM stages), and 0.9362 (III‐IV TNM stages).ConclusionsThese data represented the application of analysis of fecal colonocytes lncRNAs in early detection of CRC.     

miRNA-21在结直肠癌中的表达研究

目的 检测MicroRNA-21（miRNA-21）在正常人和结直肠癌患者血清,以及结直肠癌患者癌组织和癌旁组织中的表达,探讨其与结直肠癌临床病理参数的关系.方法 采用实时荧光定量PCR（RT-qPCR）技术检测正常人和结直肠癌患者血清,以及结直肠癌患者癌组织和癌旁组织中的表达,分析miRNA-21的表达与结直肠癌临床病理参数的关系.结果 miRNA-21在结直肠癌患者血清中表达水平显著高于正常人血清（P＜0.05）;结直肠癌组织中miRNA-21表达水平明显高于癌旁组织;中晚期（Ⅲ期和Ⅳ期）结直肠癌组织中miRNA-21表达水平明显高于早期（Ⅰ期和Ⅱ期）结直肠癌（P＜0.05）;低分化肿瘤组织中miRNA-21表达水平明显高于中高分化者;有淋巴结转移的结直肠癌组织中miRNA-21表达水平明显高于无淋巴结转移者.结论 miRNA-21在结直肠癌患者血清及肿瘤组织中呈高表达,可能与结直肠癌的发生发展有关.     

Hsa_circ_0001550 facilitates colorectal cancer progression through mediating microRNA‐4262/nuclear casein kinase and cyclin‐dependent kinase substrate 1 cascade

BackgroundCircular RNAs (circRNAs) play important roles in various malignancies, such as colorectal cancer (CRC). However, the function of hsa_circ_0001550 in CRC remains to be elucidated.MethodsThe expression levels of hsa_circ_0001550, microRNA (miR)‐4262, and nuclear casein kinase and cyclin‐dependent kinase substrate 1 (NUCKS1) were determined by real‐time qPCR. Cell biological behaviors were evaluated via colony formation assay, transwell assay, flow cytometry, and sphere formation assays. The target relationship was validated via dual‐luciferase reporter and RNA pull‐down assays. Protein expression was analyzed by western blot. Xenograft tumor model was adopted to evaluate hsa_circ_0001550 function in vivo.ResultsHsa_circ_0001550 enrichment was enhanced in CRC tissue specimens and cell lines. Hsa_circ_0001550 absence hindered CRC cell proliferation, metastasis, stemness, and caused apoptosis. Hsa_circ_0001550 targeted miR‐4262, and hsa_circ_0001550 absence‐caused impacts were diminished by anti‐miR‐4262. MiR‐4262 targeted NUCKS1. Hsa_circ_0001550 had positive regulation on NUCKS1 expression. NUCKS1 overexpression overturned the influences of hsa_circ_0001550 silencingon CRC cell progression. Hsa_circ_0001550 interference notably blocked in vivo xenograft tumor growth.ConclusionHsa_circ_0001550 facilitated CRC progression by binding to miR‐4262 to positively regulate NUCKS1 abundance.     

Hsa_circ_0031787 promotes cell proliferation and invasion in colorectal cancer

ObjectiveCircular RNA (circRNA) has been found to be involved in regulating tumor development. However, the roles and underlying mechanisms of circRNA in colorectal cancer (CRC) development remain unclear. In this study, we investigated the effects of hsa_circ_0031787 on CRC.aMethodsAberrant circRNA expression was explored by the Gene Expression Omnibus (GEO) database, and hsa_circ_0031787 was selected for further study. Hsa_circ_0031787 expression was determined in CRC tissues and cell lines by qRT‐PCR. Cell proliferation was measured by Edu and colony formation assays. Cell invasion was tested by Transwell assays.ResultsHsa_circ_0031787 expression levels in CRC were significantly increased and correlated with advanced TNM stage and lymph node metastasis in CRC patients. Functional assays showed that hsa_circ_0031787 suppression reduced CRC cell proliferation and invasion in vitro and reduced tumor growth in vivo. Furthermore, hsa_circ_0031787 suppression reduced activation of the Wnt/β‐catenin axis in CRC.ConclusionsOur results showed that hsa_circ_0031787 may function as an oncogenic circRNA in CRC progression, thus providing a new potential therapeutic target.     

Plasma circular RNA hsa_circ_0001821 acts as a novel diagnostic biomarker for malignant tumors

BackgroundCircular RNAs (circRNAs) can function as key regulators of oncogenic processes. The main purpose of this study was to evaluate the expression of hsa_circ_0001821 in plasma of patients with colorectal cancer (CRC) and other malignant tumors and analyze its correlations with clinical features and diagnostic values.MethodsIn total, 467 plasma samples, including samples from 80 healthy controls, were collected between 2015 and 2019 from patients at the Affiliated People''s Hospital of Ningbo University. Plasma levels of hsa_circ_0001821 were analyzed by qRT‐PCR. The diagnostic value was performed using receiver operating characteristic (ROC) curve.ResultsPlasma hsa_circ_0001821 was increased in CRC patients, and high hsa_circ_0001821 expression predicted advanced stage and unfavorable in overall survival. In addition, this study showed the upregulation of hsa_circ_0001821 in plasma of lung cancer and hepatocellular carcinoma (HCC). ROC curve showed that the region under the loop for the diagnosis of CRC, HCC, and lung cancer was 0.815, 0.692, and 0.792.ConclusionPlasma hsa_circ_0001821 possibly is a novel biological marker for malignant tumors.     

Meta‐analysis of the diagnostic value of exosomal miR‐21 as a biomarker for the prediction of cancer

BackgroundEarly diagnosis of cancer is still the most effective method to increase survival and therapeutically effective patient management. Accumulating studies had exploited exosomes as an indicator for the diagnosis and prognosis of cancer. In addition to exosomes, exosome‐derived miRs are widely investigated as a novel biomarker for diagnosis in cancer patients. The aim of this study was to clarify the diagnostic value of ex‐miR‐21 in cancer.MethodsDatabases were searched for eligible studies up to June, 2021. Studies included in this meta‐analysis were reviewed and selected independently by two authors. The data of sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic curves (SROC) of exosomal miR‐21 as a diagnostic biomarker were extracted and calculated. Quality assessment was conducted by using the QUADAS‐2 tool.ResultsA total of 26 studies were included in the systematic analysis and meta‐analysis. The pooled results of sensitivity, specificity, PLR/NLR, DOR, and area under the curve were 76% (95%CI, 0.70–0.81), 82% (0.77–0.87), 4.3 (3.1–6.0), 0.29 (0.22–0.38), 15 (8–26), and 0.86 (0.83–0.89), respectively. Sensitivity analysis and Deeks'' funnel plot indicated that results remained unchanged and had no publication bias. For the subgroup analysis, it was showed that ex‐miR‐21 had a superior diagnostic accuracy on identifying PC.ConclusionExosomal microRNA‐21 can serve as an effective and widely used diagnostic biomarker for cancer, especially in PC. The using field of exosomes and exosome‐derived miR can further extend the prognosis and therapeutic management. Standardized isolation of exosomes and miRNA‐21 should be developed.     

Serum Circ‐FAF1/Circ‐ELP3: A novel potential biomarker for breast cancer diagnosis

BackgroundRecently, measurement of serum circular RNAs (circRNAs) as a non‐invasive tumor marker has been considered more. We designed the present study to investigate the diagnostic efficiency of serum Circ‐ELP3 and Circ‐FAF1, separately and simultaneously, for diagnosis of patients with breast cancer.MethodsSeventy‐eight female patients diagnosed as primary breast cancer participated in this study. We measured the level of circRNAs in serum specimens of the studied subjects. A receiver operating characteristic (ROC) curve was plotted and the diagnostic efficiency for both circRNAs was determined.ResultsCompared to non‐cancerous controls, Circ‐ELP3 was upregulated in breast cancer patients (p‐value = 0.004). On the other hand, serum Circ‐FAF1 was seen to be decreased in breast cancer patients than controls (p‐value = 0.001). According to ROC curve results, the area under the curve (AUC) for Circ‐ELP3 and Circ‐FAF1 was 0.733 and 0.787, respectively. Furthermore, the calculated sensitivity and specificity for Circ‐ELP3 and Circ‐FAF1 were 65, 64% and 77, 74%, respectively. Merging both circRNAs increased the diagnostic efficiency, with a better AUC, sensitivity and specificity values of 0.891, 96 and 62%, respectively.ConclusionBriefly, our results revealed the high diagnostic value for combined circRNAs panel, including Circ‐ELP3 and Circ‐FAF1 as a non‐invasive marker, in detection of breast carcinomas.     

Serum N‐glycan profiling as a diagnostic biomarker for the identification and assessment of psoriasis

BackgroundGlycosylation is an important post‐translational modification of protein. The change in glycosylation is involved in the occurrence and development of various diseases, and this study verified that N‐glycan markers might be a diagnostic marker in psoriasis.MethodsA total of 76 psoriasis patients were recruited. We used Psoriasis Area Severity Index (PASI) scores to evaluate the state of psoriasis, 41 of whom were divided into three subgroups: mild, moderate, and severe. At the same time, 76 healthy subjects were enrolled as a control group. We used DNA sequencer–assisted fluorophore‐assisted carbohydrate electrophoresis (DSA‐FACE) to analyze serum N‐glycan profiling.ResultsCompared with the healthy controls, the relative abundance of structures in peaks 5(NA2), 9(NA3Fb), 11(NA4), and 12(NA4Fb) was elevated (p < .05), while that in peaks 3(NG1A2F), 4(NG1A2F), 6(NA2F), and 7(NA2FB) was decreased (p < .05) in the psoriasis group. The abundance of peak 5 (NA2) increased gradually with the aggravation of disease severity though there was no statistically significant, was probably correlated with the disease severity. The best area under the receiver operating characteristic (ROC) curve (AUC) of the logistic regression model (PglycoA) to diagnose psoriasis was 0.867, with a sensitivity of 72.37%, a specificity of 85.53%, a positive predictive value(PPV) of 83.33%, a negative predictive value(NPV) of 75.58%, and an accuracy of 78.95%.ConclusionsOur study indicated that the N‐glycan–based diagnostic model would be a new, valuable, and noninvasive alternative for diagnosing psoriasis. Furthermore, the characteristic distinctive N‐glycan marker might be correlated with the severity gradation of the psoriasis disease.     

Identification of Cofilin‐1 as a novel biomarker of atopic dermatitis using iTRAQ quantitative proteomics

BackgroundAtopic dermatitis (AD) is a chronic relapsing inflammatory skin condition; however, little is known about the pathogenesis and serum biomarker of this disease.MethodsIsobaric tagging for relative and absolute quantitation (iTRAQ) proteomic assay was adopted to identify and quantify the differentially expressed proteins (DEPs) in the serum of AD patients. Bioinformatic analysis, including GO, Reactome, GSEA, PPI, and ssGSEA analysis, were used to identified the enriched pathways, hub proteins and immune cells. The expression level and distribution of hub proteins were confirmed by ELISA and IHC.ResultsSixty‐six DEPs were identified with iTRAQ proteomic assay by analyzing serum from AD patients and normal subjects. GO and Reactome analysis shown the alternated pathway were mainly involved in immunity, oxidative stress, and actin cytoskeleton. The GSEA and PPI network analysis among the DEPs were carried out and identified Cofilin‐1 and profilin‐1 as the core components of this network. Additionally, the disruption of Th1/Th2/Th17 cell balance and the significantly reducing of Treg, MDSC, and γδT cells was also found in AD patients using the ssGSEA analysis. Further ELISA and IHC assay validated the significantly elevated expression of Cofilin‐1 in AD patients.ConclusionOur results suggested that Cofilin‐1 may serve as a novel biomarker for AD diagnosis.