Search

Background: Esophageal cancer (EC) is highly ranked among all cancers in terms of its incidence and mortality rates. MicroRNAs (miRNAs) are considered to play key regulatory parts in EC. Multiple research studies have indicated the involvement of miR-3682-3p and four and a half LIM domain protein 1 (FHL1) in the achievement of tumors. The aim of this research was to clarify the significance of these genes and their possible molecular mechanism in EC., Methods: Data from a database and the tissue microarray were made to analyze the expression and clinical significance of miR-3682-3p or FHL1 in EC. Reverse transcription quantitative PCR and Western blotting were used to detect the expression levels of miR-3682-3p and FHL1 in EC cells. CCK8, EdU, wound healing, Transwell, flow cytometry, and Western blotting assays were performed to ascertain the biological roles of miR-3682-3p and FHL1 in EC cells. To confirm the impact of miR-3682-3p in vivo, a subcutaneous tumor model was created in nude mice. The direct interaction between miR-3682-3p and FHL1 was demonstrated through a luciferase assay, and the western blotting technique was employed to assess the levels of crucial proteins within the Wnt/β-catenin pathway., Results: The noticeable increase in the expression of miR-3682-3p and the decrease in the expression of FHL1 were observed, which correlated with a negative impact on the patients' overall survival. Upregulation of miR-3682-3p expression promoted the growth and metastasis of EC, while overexpression of FHL1 partially reversed these effects. Finally, miR-3682-3p motivates the Wnt/β-catenin signal transduction by directly targeting FHL1., Conclusion: MiR-3682-3p along the FHL1 axis activated the Wnt/β-catenin signaling pathway and thus promoted EC malignancy., Competing Interests: Declaration of competing interest The authors declare no potential competing of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Long non-coding RNAs (lncRNAs), tentatively identified as non-protein coding RNA, are transcripts more than 200nt in length and accounting for 98% of the whole genome of human being. Accumulating evidence showed aberrant expressions of lncRNAs are strongly correlated to the development of cancers. In this study, AF113014 is a new lncRNA identified from Microarray. We found AF113014 is differentially expressed between HCC cell lines and normal hepatocytes. Functionally, AF113014 inhibited proliferation of HCC cells both in vitro and in vivo, whereas the opposite effect was observed when AF113014 knockdown. Moreover, we identified that Egr2, a tumor suppressor gene, was a downstream target gene of AF113014. Furthermore, we discovered that AF113014 up-regulated Egr2 expression through interacting with miR-20a by using dual-luciferase reporter assay, qRT-PCR and Western blotting analysis. Our data provides a new insight for understanding the mechanisms of HCC.

Resveratrol, as a natural product compound, has been recently attracted much attention for its potent effects on cancer. Cancer is a serious disease threatening human survival and social development. Autophagy is a cellular pathway to realize the metabolic needs of the cell itself and the renewal of some organelles and plays opposing, context-dependent role in tumorigenesis. So the regulation of autophagy is of great significance in the treatment of cancer. p62, as an autophagy adaptor protein, is a preferred target for autophagy and is constantly controlled by constitutive autophagy. As a tumor-suppression mechanism, autophagy deficiency is common in tumors, which results in aberrant accumulation of p62 and activates p62-regulated pathways, such as activation of mTOR in nutrient sensing, and the activation of the Keap1-Nrf2 pathway for antioxidant stress, which are associated with cancer development. In this review, we emphasize that resveratrol can induce autophagy in the treatment of cancer and accelerates the degradation of p62, and then, the mTOR activation is blocked and Nrf2 activation is suppressed. As a result, the multidrug resistance of cancer cells can be reversed by resveratrol. [ABSTRACT FROM AUTHOR]

BACKGROUNDS: MicroRNAs (miRNAs) are some RNA molecules that negatively regulate gene expression by binding to the 3’-untranslated region (3’-UTR) of target mRNA molecules. The aim of the study is to investigate the clinical role and functional effects of microRNA-493 (miR-493) in human hepatocellular carcinoma (HCC). METHODS: Expression of miR-493 in 58 cases of HCC tissues and adjacent normal tissues was determined by using quantitative real-time PCR (qRT-PCR) analyses. In vitro, cell proliferation and invasion capacity was evaluated by CCK8 assay and trans-well invasion assay. Luciferase reporter assay, western blot and qRT-PCR were used to detect the association between miR-493 expression and zinc finger protein X-linked (ZFX) in HCC. RESULTS: Expression of miR-493 was significantly downregulated in HCC tissues compared to adjacent normal tissues. Lower miR-493 expression associated with tumor size, vascular invasion and poor overall survival (OS) and disease free survival (DFS) time of HCC patients. In vitro, transfection of miR-493 mimic in HCC cells inhibited cell proliferation and invasion abilities. However, transfection of miR-493 inhibitor in HCC cells had promoting effects. Luciferase reporter assay, qRT-PCR and western blot analysis demonstrated that miR-493 targeting 3’-untranslated region (3’-UTR) of ZFX and overexpression of miR-493 inhibited its expression. Moreover, enforced ZFX expression rescued the effects of miR-493 mimic on cell proliferation and invasion. CONCLUSION: MiR-493 functioned as tumor suppressor in HCC cells by regulating ZFX expression. Thus, miR-493 may provide potential value for HCC treatment. [ABSTRACT FROM AUTHOR]

Background: Signal transducer and activator of transcription 3 (Stat3) is known to induce cell proliferation and inflammation by regulating gene transcription. Recent studies showed that Stat3 modulates nociceptive transmission by reducing spinal astrocyte proliferation. However, it is unclear whether Stat3 also contributes to the modulation of nociceptive transmission by regulating inflammatory response in spinal astrocytes. This study aimed at investigating the role of Stat3 on neuroinflammation during development of pain in rats after intrathecal injection of lipopolysaccharide (LPS). Methods: Stat3 specific siRNA oligo and synthetic selective inhibitor (Stattic) were applied to block the activity of Stat3 in primary astrocytes or rat spinal cord, respectively. LPS was used to induce the expression of proinflammatory genes in all studies. Immunofluorescence staining of cells and slices of spinal cord was performed to monitor Stat3 activation. The impact of Stat3 inhibition on proinflammatory genes expression was determined by cytokine antibody array, enzyme-linked immunosorbent assay and real-time polymerase chain reaction. Mechanical allodynia, as determined by the threshold pressure that could induce hind paw withdrawal after application of standardized von Frey filaments, was used to detect the effects of Stat3 inhibition after pain development with intrathecal LPS injection. Results: Intrathecal injection of LPS activated Stat3 in reactive spinal astrocytes. Blockade of Stat3 activity attenuated mechanical allodynia significantly and was correlated with a lower number of reactive astrocytes in the spinal dorsal horn. In vitro study demonstrated that Stat3 modulated inflammatory response in primary astrocytes by transcriptional regulation of chemokine expression including Cx3cl1, Cxcl5, Cxcl10 and Ccl20. Similarly, inhibition of Stat3 reversed the expression of these chemokines in the spinal dorsal horn. Conclusions: Stat3 acted as a transcriptional regulator of reactive astrocytes by modulating chemokine expression. Stat3 regulated inflammatory response in astrocytes and contributed to pain modulation. Blockade of Stat3 represents a new target for pain control. [ABSTRACT FROM AUTHOR]

• CDKN2B-AS1 level was negatively correlated with levels of inflammatory cytokines. • miR-16-5p and miR-195-5p levels were negatively correlated with the CDKN2B-AS1 level. • pcDNA-CDKN2B-AS1 depressed expressions of IFN-γ, IL-8, IL-1β and TNF-α and strengthened viability and proliferation ability. • CDKN2B-AS1 also sponged and regulated miR-16-5p and miR-195-5p. This study was aimed to explore the differential expression of lncRNA CDKN2B-AS1-miR-195-5p/miR-16-5p axis in ulcerative colitis (UC) and its role in regulating UC pathogenesis. One hundred and eighty-seven UC patients and one hundred and fifty-two healthy volunteers were recruited, and their blood samples were collected. Inflammatory cytokines in serum were determined with ELISA, and lncRNA CDKN2B-AS1, miR-195-5p and miR-16-5p levels were detected with RT-PCR. Then pcDNA3.1-CDKN2B-AS1, si-CDKN2B-AS1, miR-195-5p mimic, miR-195-5p inhibitor, miR-16-5p mimic and miR-16-5p inhibitor were transfected into HT29 cells, and proliferation and apoptosis of the cells were assessed. Dual-luciferase reporter gene assay was implemented to identify the sponging relationship between lncRNA CDKN2B-AS1 and miR-195-5p/miR-16-5p. CDKN2B-AS1 level was negatively correlated with levels of inflammatory cytokines, including TNF-α, IL-6 and sIL-2R, yet miR-16-5p and miR-195-5p levels were negatively correlated with the CDKN2B-AS1 level. The CDKN2B-AS1 combined with miR-16-5p and miR-195-5p also achieved an optimum efficacy in differentiating between light and medium UC, light and severe UC, as well as medium and heavy UC. Furthermore, pcDNA3.1-CDKN2B-AS1 depressed expressions of IFN-γ, IL-8, IL-1β and TNF-α in HT29 cells (P < 0.05), and strengthened proliferation of the cells (P < 0.05). CDKN2B-AS1 also sponged and regulated miR-16-5p and miR-195-5p in HT29 cells, and miR-16-5p and miR-195-5p could reverse the effect of CDKN2B-AS1 on inflammatory cytokine production, barrier function and apoptosis of HT29 cells (P < 0.05). LncRNA CDKN2B-AS1 regulated inflammation of UC by sponging miR-195-5p and miR-16-5p, providing an alternative for diagnosis and treatment of UC. [ABSTRACT FROM AUTHOR]