Recent studies have indicated the possible function of miR-217 in tumorigenesis. However, the roles of miR-217 in colorectal cancer (CRC) are still largely unknown. We examined the expression of miR-217 and AEG-1 in 50 CRC tissues and the corresponding noncancerous tissues by qRT-PCR. The clinical significance of miR-217 was analyzed. CRC cell lines with miR-217 upregulation and AEG-1 silencing were established and the effects on tumor growth in vitro and in vivo were assessed. Dual-luciferase reporter gene assays were also performed to investigate the interaction between miR-217 and AEG-1. Our data demonstrated that miR-217 was significantly downregulated in 50 pairs of colorectal cancer tissues. MiR-217 expression levels were closely correlated with tumor differentiation. Moreover, decreased miR-217 expression was also associated with shorter overall survival of CRC patients. MiR-217 overexpression significantly inhibited proliferation, colony formation and invasiveness of CRC cells by promoting apoptosis and G0/G1 phase arrest. Interestingly, ectopic miR-217 expression decreased AEG-1 expression and repressed luciferase reporter activity associated with the AEG-1 3′-untranslated region (UTR). AEG-1 silencing resulted in similar biological behavior changes to those associated with miR-217 overexpression. Finally, in a nude mouse xenografted tumor model, miR-217 overexpression significantly suppressed CRC cell growth. Our findings suggest that miR-217 has considerable value as a prognostic marker and potential therapeutic target in CRC.

The role of long non-coding RNAs (lncRNAs) in colorectal cancer (CRC) progression has not fully been elucidated. This study was designed to report the identification of a novel lncRNA, lnc-GNAT1-1, and its functional role in CRC progression. lncRNA expression profile microarray was performed in three paired primary and liver metastatic tissues of CRC, and a novel lncRNA, lnc-GNAT1-1, was identified to be a potential functional lncRNA. Quantitative real-time PCR was used to detect its expression in CRC tissues, cell lines, and patients’ plasma, cell fractionation was used to evaluate its subcellular location. lnc-GNAT1-1 was knockdown by siRNA or overexpressed by a lentivirus vector, then in vitro an vivo experiments were performed to evaluate its biological role and the underlying mechanisms in CRC. Expression of lnc-GNAT1-1 was decreased in liver metastasis than the primary tumor, while the later one is lower than the paired normal mucosa. Decreased lnc-GNAT1-1 expression was associated unfavorable clinicopathological features and a poor prognosis of CRC patients. In multivariate analysis, lnc-GNAT1-1 was proved to be an independent prognostic factor. In plasma, lnc-GNAT1-1 was significant decreased in CRC patients than healthy donors, and with the TNM stages advanced, the plasma lnc-GNAT1-1 level decreased; Receiver operating characteristic curve (ROC curve) showed that plasma lnc-GNAT1-1 had a moderate to well diagnostic efficiency for CRC. In vitro experiments showed that knockdown of lnc-GNAT1-1 could inhibit the aggressive phenotypes of CRC cell lines. In vivo study showed that overexpression of lnc-GNAT1-1 could suppress the liver metastasis of CRC cells. Finally, we explored the underlying mechanism of the role lnc-GNAT1-1 plays in CRC, and found a positive correlation between lnc-GNAT1-1 and Raf kinase inhibitor protein (RKIP) expression both in cells and in patients’ tissues. We further found that lnc-GNAT1-1 could regulate the RKIP-NF-κB-Snail circuit in CRC. We have demonstrated in this study that a novel lncRNA, lnc-GNAT1-1, is low expressed in colorectal cancer tissues and plasma, and acts as a tumor suppressor through regulating RKIP-NF-κB-Snail circuit.

Background: As single-cell sequencing technology has been gradually introduced, it is essential to characterize global collaboration networks and map development trends over the past 20 years. Objective: The aim of this paper was to illustrate collaboration in the field of single-cell sequencing methods and explore key topics and future directions. Methods: Bibliometric analyses were conducted with CiteSpace and VOSviewer software on publications prior to November 2019 from the Web of Science Core Collection about single-cell sequencing methods. Results: Ultimately, we identified 2489 records, which were published in 495 journals by 14,202 authors from 1970 institutes in 61 countries. There was a noticeable increase in publications in 2014. The United States and high-income countries in Europe contributed to most of the records included. Harvard University, Stanford University, Karolinska Institutes, Peking University, and the University of Washington were the biggest nodes in every cluster of the collaboration network, and SA Teichmann, JC Marioni, A Regev, and FC Tang were the top-producing authors. Keywords co-occurrence analysis suggested applications in immunology as a developing research trend. Conclusions: We concluded that the global collaboration network was unformed and that high-income countries contributed more to the rapidly growth of publications of single-cell sequencing technology. Furthermore, the application in immunology might be the next research hotspot and developmental direction.

ObjectiveThe goal of this study was to get preliminary insight on the intra-tumor heterogeneity in colitis-associated cancer (CAC) and to reveal a potential evolutionary trajectory from ulcerative colitis (UC) to CAC at the single-cell level. MethodsFresh samples of tumor tissues and adjacent UC tissues from a CAC patient with pT3N1M0 stage cancer were examined by single-cell RNA sequencing (scRNA-seq). Data from The Cancer Genome Atlas (TCGA) and The Human Protein Atlas were used to confirm the different expression levels in normal and tumor tissues and to determine their relationships with patient prognosis. ResultsUltimately, 4,777 single-cell transcriptomes (1,220 genes per cell) were examined, of which 2,250 (47%) and 2,527 (53%) originated from tumor and adjacent UC tissues, respectively. We defined the composition of cancer-associated stromal cells and identified six cell clusters, including myeloid, T and B cells, fibroblasts, endothelial and epithelial cells. Notable pathways and transcription factors involved in these cell clusters were analyzed and described. Moreover, the precise cellular composition and developmental trajectory from UC to UC-associated colon cancer were graphed, and it was predicted that CD74, CLCA1, and DPEP1 played a potential role in disease progression. ConclusionsscRNA-seq technology revealed intra-tumor cell heterogeneity in UC-associated colon cancer, and might provide a promising direction to identify novel potential therapeutic targets in the evolution from UC to CAC.

Background: Alimentary tract duplications are rare congenital lesions, and only 2–8% of them are located in the stomach. Gastric duplications (GD) can lead to severe adverse events. Thus, surgical resection is required once the disease is diagnosed. The main purpose of this study is to describe the clinical features of gastric duplications and to provide evidence for the diagnosis and treatment.Methods: A retrospective review of eight gastric duplications at two medical centers Peking University People’s Hospital (PKUPH) and Shandong Provincial Hospital from 2010 to 2020 was conducted. Furthermore, the literature search was also conducted by retrieving data from PubMed, EMBASE and Cochrane Library databases from the date of the database inception to January 15, 2021.Results: Eight patients who were diagnosed as gastric duplications and 311 published records were included in this study. In all, 319 patients were identified: Vomiting and abdominal pain were the most frequent clinical presentations among juveniles and adults respectively. There was no difference in gender distribution (F: 53.16% vs M: 46.84%), and the cystic gastric duplications were the most common type of the gastric duplications (87.04%). More than half (53.30%) of included cases were located in the greater curvature of stomach.Conclusions: Gastric duplications could present with a wide spectrum of symptomatology, which might be misdiagnosed easily as other diseases. For cystic gastric duplications, the optimal treatment was a complete surgical removal. But conservative treatment might be an alternative strategy for tubular gastric duplications.

Genome-wide association study identifies two new susceptibility loci for colorectal cancer at 5q23.3 and 17q12 in Han Chinese