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Colorectal cancer (CRC) is a fatal disease ranking the third among the commonplace cancer types around the world. It is extremely significant to exploit effective treatments against CRC. FAM225A was proved to influence cell progression and forecast unfavorable prognosis in nasopharyngeal carcinoma. The role and function mechanism of FAM225A are still unclear in CRC. In this research, FAM225A was discovered presenting much higher expression in CRC tissues and cell lines. In addition, depleting FAM225A was capable of inhibiting cell proliferation, migration, and epithelial‐to‐mesenchymal transition (EMT) progress, and enhancing cell apoptosis ability. Furthermore, miR‐613 exerted important effects as a mediator between FAM225A and NOTCH3. NOTCH3 was negatively correlated with miR‐613, whereas was positively associated with FAM225A. Via competitively binding with miR‐613, FAM225A positively regulated NOTCH3 expression. FAM225A facilitated CRC occurrence and development through positively regulating NOTCH3 expression by binding with miR‐613. In a word, FAM225A/miR‐613/NOTCH3 axis may play a tumor‐facilitator in CRC cell progression. These data manifested the pivotal effect of FAM225A/miR‐613/NOTCH3 pathway in CRC cell proliferation, apoptosis, and migration process. The findings may provide some theoretical basis and different perspective for CRC treatment., FAM225A presents high expression in CRC tissues and cell lines. FAM225A expedites CRC cell proliferation, migration abilities, and impairs cell apoptosis capacity. FAM225A acts as a sponge of miR‐613 and is negatively correlated with miR‐613.

A widely recognized feature of colorectal cancer (CRC) is an increase in cytokine levels, which result in an inflammatory environment in the tumor. Interleukin-6 (IL-6) is a robust protumor cytokine. Several studies suggest that IL-6 plays a role in the development of tumors. Most intracellular protein breakdown occurs in eukaryotes via the ubiquitin-proteasome pathway; this mechanism may also be involved in cancer pathogenesis. The tumor tissues and paracancerous tissues were collected from 90 patients with colorectal cancer. The expressions of pSTAT3, proteasome 20S

Circular RNAs (circRNAs) have been reported to play crucial roles in the progression of various cancers, including colorectal cancer (CRC). SP1 (Sp1 transcription factor) is a well-recognized oncogene in CRC and is deemed to trigger the Wnt/β-catenin pathway. The present study was designed to investigate the role of circRNAs which shared the same pre-mRNA with SP1 in CRC cells. We identified that hsa_circ_0026628 (circ_0026628), a circular RNA that originated from SP1 pre-mRNA, was upregulated in CRC cells. Sanger sequencing and agarose gel electrophoresis verified the circular characteristic of circ_0026628. Functional assays including CCK-8, colony formation, transwell, immunofluorescence staining, and sphere formation assay revealed the function of circ_0026628. RNA pull-down and mass spectrometry disclosed the proteins interacting with circ_0026628. Mechanistic assays including RIP, RNA pull-down, CoIP, ChIP, and luciferase reporter assays demonstrated the interplays between molecules. The results depicted that circ_0026628 functioned as a contributor to CRC cell proliferation, migration, EMT, and stemness. Mechanistically, circ_0026628 served as the endogenous sponge of miR-346 and FUS to elevate SP1 expression at the post-transcriptional level, thus strengthening the interaction between SP1 and β-catenin to activate the Wnt/β-catenin pathway. In turn, the downstream gene of Wnt/β-catenin signaling, SOX2 (SRY-box transcription factor 2), transcriptionally activated SP1 and therefore boosted circ_0026628 level. On the whole, SOX2-induced circ_0026628 sponged miR-346 and recruited FUS protein to augment SP1, triggering the downstream Wnt/β-catenin pathway to facilitate CRC progression.

BACKGROUND The formation of liver fibrosis is mainly caused by the activation of hepatic stellate cells (HSCs) and the imbalance of extracellular matrix (ECM) production and degradation. The treatment of liver fibrosis mainly includes removing the cause, inhibiting the activation of HSCs, and inhibiting inflammation. NOD-like receptor (NLR) family, caspase activation and recruitment domain (CARD) domain containing 5/NOD27/CLR16.1 (NLRC5) is a highly conserved member of the NLR family and is involved in inflammation and immune responses by regulating various signaling pathways such as nuclear factor-κB (NF-κB) signaling. It has been found that NLRC5 plays an important role in liver fibrosis, but its specific effect and possible mechanism remain to be fully elucidated. AIM To investigate the role of NLRC5 in the activation and reversion of HSCs induced with transforming growth factor-β (TGF-β) and MDI, and to explore its relationship with liver fibrosis. METHODS A total of 24 male C57BL/6 mice were randomly divided into three groups, including normal, fibrosis, and recovery groups. Twenty-four hours after a liver fibrosis and spontaneous reversion model was established, the mice were sacrificed and pathological examination of liver tissue was performed to observe the degree of liver fibrosis in each group. LX-2 cells were cultured in vitro and treated with TGF-β1 and MDI. Real-time quantitative PCR (qPCR) and Western blot were used to analyze the expression levels of NLRC5, α-smooth muscle actin (α-SMA), and collagen type I alpha1 (Col1a1) in each group. The activity of NF-κB in each group of cells transfected with NLRC5-siRNA was detected. RESULTS Compared with the normal mice, the expression level of NLRC5 increased significantly (P < 0.01) in the fibrosis group, but decreased significantly in the recovery group (P < 0.01). In in vitro experiments, the content of NLRC5 was enhanced after TGF-β1 stimulation and decreased to a lower level when treated with MDI (P < 0.01). The expression of α-SMA and Col1a1 proteins and mRNAs in TGF-β1-mediated cells was suppressed by transfection with NLRC5-siRNA (P < 0.01). Western blot analysis showed that the expression of NF-κB p65 protein and phosphorylated IκBα (p-IκBα) was increased in the liver of mice in the fibrosis group but decreased in the recovery group (P < 0.01), and the protein level of nuclear p65 and p-IκBα was significantly increased after treatment with NLRC5-siRNA (P < 0.01). CONCLUSION NLRC5 may play a key role in the development and reversal of hepatic fibrosis through the NF-κB signaling pathway, and it is expected to be one of the clinical therapeutic targets.

The present study aims to determine the potential biomarkers and uncover the regulatory mechanisms of the long-noncoding RNA (lncRNA) TINCR/miR-107/CD36 axis in colorectal cancer (CRC). Aberrantly-expressed lncRNAs and differential-expressed genes were identified by analyzing the dataset GSE40967. Gene set enrichment analysis was employed, and Cytoscape software helped in establishing the co-expression network between lncRNAs and genes. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis contributes to examining the expression levels of lncRNA TINCR, miR-107 and CD36. The dual luciferase assay was used to validate the association between miR-107 and lncRNA TINCR or CD36. The EdU incorporation assay was employed, and flow cytometry was employed to detect cell apoptosis with the tumor xenograft model being utilized. Significantly dysregulated lncRNAs and mRNAs were identified. The peroxisome proliferator-activated receptor (PPAR) signaling pathway in CRC tissues was down-regulated. The loss of TINCR expression was associated with CRC progression. The expression levels of the TINCR and CD36 were down-regulated. We identified miR-107 as an inhibitory target of TINCR and CD36. Overexpression of TINCR could inhibit cell proliferation and promote apoptosis. MiR-107 overexpression in CRC cells induced proliferation and impeded apoptosis. A regulatory function of the lncRNA TINCR/miR-107/CD36 axis in CRC was revealed. LncRNA TINCR overexpression exerted suppressive influence on CRC progression through modulating the PPAR signaling pathway via the miR-107/CD36 axis.

To explore the expression of CD160, a costimulator, on CD4(+) and CD8(+) T cells in chronic human immunodeficiency virus-1 (HIV-1) infected patients.A total of 23 chronic HIV-1 infected patients were enrolled into 302 Hospital of People's Liberation Army from January 2010 to December 2011. Meanwhile, 20 healthy individuals were selected as healthy controls (HC). Peripheral blood was collected, peripheral blood mononuclear cells (PBMC) were isolated by density gradient centrifugation and CD160 was stained with fluorescent antibody. The expressions of CD160 on CD4(+) and CD8(+) T cell subsets were detected by flow cytometry and its correlation with CD4(+) T cell absolute number and HIV RNA viral load were analyzed.The expressions of CD160 on CD4(+) and CD8(+) T cell increased versus HC (on CD4(+) T cells, percentage: (14.3 ± 7.5)% vs (3.9 ± 2.2)%, median fluorescent intensity (MFI): 26.4 ± 11.0 vs 12.4 ± 2.9; on CD8(+) T cells, percentage: (40.9 ± 13.2)% vs (12.9 ± 6.6)%, MFI: 52.5 ± 17.4 vs 18.2 ± 5.0). Furthermore, the expression of CD160 on CD4(+) T cells was negatively correlated with CD4(+) T cell absolute number (r = -0.550, P = 0.010) and positively with HIV RNA load (r = 0.522, P = 0.015). However, the expression of CD160 on CD8(+) T cells was not correlated with CD4(+) T cell absolute number or HIV RNA load. The expressions of CD160 on CD8(+) T cell subsets Tn, Tcm and Tem in patients with chronic HIV-1 infection increased compared with HC (25.3 ± 17.6 vs 5.0 ± 3.1, 45.8 ± 13.0 vs 20.4 ± 4.3, 37.0 ± 13.6 vs 20.0 ± 10.8). In addition, Tn subset decreased while Tcm subset increased in CD160(+) CD8(+) T cell subset distribution in patients with HIV-1 infection compared with HC subjects.CD160 may contribute to the exhaustion of CD4(+) and CD8(+) T cells and influence the distribution of memory CD8(+) T cell subsets.