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The article "Overexpression of long non-coding RNA TUG1 alleviates TNF-α-induced inflammatory injury in interstitial cells of Cajal", by K. Zhao, J.-Y. Tan, Q.-D. Mao, K.-Y. Ren, B.-G. He, C.-P. Zhang, L.-Z. Wei published in Eur Rev Med Pharmacol Sci 2019; 23 (1): 312-320-DOI: 10.26355/eurrev_201901_16778-PMID: 30657572 has been retracted by the authors for the following reasons: We are still conducting research in the effect of long non-codingRNA TUG1 in interstitial cells of Cajal recently. It turned out that some of the current experimental results are inconsistent with the previous results. Some data cannot be repeated by further research. We need to further confirm the effect of long non-coding RNA TUG1 on alleviating TNF-α-induced inflammatory injury in interstitial cells of Cajal and for this reason, the authors all agreed to withdraw the manuscript. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/16778.
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OBJECTIVE: Irritable bowel syndrome (IBS) is a common functional disorder in the gastrointestinal tract. Inflammatory response has been found to participate in the pathogenesis of IBS. This study aimed to explore the effects of long non-coding RNA taurine upregulated gene 1 (TUG1) on tumor necrosis factor alpha (TNF-α)-induced interstitial cells of Cajal (ICC) inflammatory injury, which was relevant to the pathogenesis of IBS. PATIENTS AND METHODS: The expression levels of TUG1 and microRNA-127 (miR-127) were analyzed by qRT-PCR. Viability, apoptosis and the expression of apoptosis-associated factors were analyzed by CCK-8 assay, flow cytometry and Western blot, respectively. The mRNA and protein levels of pro-inflammatory cytokines were detected by qRT-PCR and Western blot, respectively. Finally, activations of nuclear factor kappa-B (NF-κB) and Notch pathways were evaluated by Western blot. RESULTS: TNF-α treatment inhibited ICC viability, induced ICC apoptosis and promoted an inflammatory response in ICC. TUG1 was downregulated in TNF-α-treated ICC. TUG1 overexpression protected ICC from TNF-α-induced apoptosis and pro-inflammatory cytokines expression. TUG1 suppression showed opposite effects. MiR-127 was negatively regulated by TUG1 and implicated in the action of TUG1 in ICC. MiR-127 up-regulation largely reversed the effects of TUG1 on TNF-α-treated ICC. Mechanistically, TUG1 inhibited TNF-α-induced activation of NF-κB and Notch pathways in ICC by down-regulating miR-127. CONCLUSIONS: TUG1 attenuated TNF-α-caused apoptosis and inflammatory response in ICC by down-regulating miR-127 and then inactivating NF-κB and Notch pathways.
Assuntos
Células Intersticiais de Cajal/imunologia , Síndrome do Intestino Irritável/genética , MicroRNAs/genética , RNA Longo não Codificante/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Apoptose/genética , Apoptose/imunologia , Sobrevivência Celular/genética , Sobrevivência Celular/imunologia , Células Cultivadas , Feminino , Perfilação da Expressão Gênica , Humanos , Células Intersticiais de Cajal/patologia , Síndrome do Intestino Irritável/imunologia , Síndrome do Intestino Irritável/patologia , Camundongos , MicroRNAs/metabolismo , Cultura Primária de Células , RNA Longo não Codificante/agonistas , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Receptores Notch/imunologia , Receptores Notch/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Fator de Necrose Tumoral alfa/imunologia , Regulação para CimaRESUMO
OBJECTIVE: Clostridium butyricum (C. butyricum) as a probiotic has been reported to have an important role in the pathogenesis of gastrointestinal diseases. However, the effects of C. butyricum on regulation of intestinal motility of ulcerative colitis (UC) remain unclear. Our study aimed to explore the cross-regulation effect of C. butyricum and toll-like receptor 2 (TLR-2) on UC. MATERIALS AND METHODS: Interstitial cells of Cajal (ICCs) were treated by C. butyricum for 2 h, the mRNA and protein levels of TLR-2, IL-6, and IL-8 were detected by RT-qPCR and Western blot. Then, TLR2-specific small interfering RNA (si-TLR2) was transfected into ICCs, and the relative expressions of IL-6 and IL-8, SCF, cell viability, ghrelin, SP, and ET were measured by RT-qPCR, Western blot, CCK-8, and ELISA. Besides, the signal pathways of NF-κB and JNK were determined by Western blot. RESULTS: C. butyricum significantly increased TLR2, IL-6, and IL-8 expressions in ICCs. However, TLR2 silence alleviated C. butyricum-induced IL-6 and IL-8 expressions. Moreover, TLR2 silence significantly inhibited C. butyricum-induced cell viability in ICCs. Additionally, C. butyricum significantly increased SCF expression and promoted the secretion of ghrelin and SP. However, a significant reduction in the levels of SCF, ghrelin, and SP was evident in the silence of TLR2 expression. Besides, TLR2 silence reduced C. butyricum-activation NF-κB and JNK signal pathways in ICCs. CONCLUSIONS: These findings revealed that C. butyricum promoted intestinal motility by regulation of TLR2 in ICCs, which contributed to understand the molecular mechanisms of C. butyricum on UC.
Assuntos
Clostridium butyricum , Colite Ulcerativa/tratamento farmacológico , Motilidade Gastrointestinal/efeitos dos fármacos , Células Intersticiais de Cajal/efeitos dos fármacos , Probióticos/farmacologia , Receptor 2 Toll-Like/fisiologia , Colite Ulcerativa/imunologia , Colite Ulcerativa/fisiopatologia , Motilidade Gastrointestinal/fisiologia , Regulação da Expressão Gênica , Humanos , NF-kappa B/fisiologia , Probióticos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Receptor 2 Toll-Like/genéticaRESUMO
Colorectal cancer (CRC) is the fourth leading cause of cancer-induced mortality. Histone deacetylase 2 (HDAC2) is involved in prognosis and therapy of CRC. This study aimed to explore novel therapeutic targets for CRC. The alteration of HDAC2 expression in CRC tissues was estimated by qRT-PCR. After lentivirus transfection, HDAC2 knockdown was confirmed by western blot analysis. The effect of HDAC2 knockdown on cell proliferation was then assessed by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Screened by TargetScan, microRNA (miR)-455 was predicted to bind to 3′UTR of HDAC2 and the prediction was verified by luciferase assay. Finally, cells were transfected, respectively, with miR-455 mimics or miR-455 negative control (miR-NC) and the expression of HDAC2, cell proliferation and apoptosis of transfected cells were respectively evaluated by western blot analysis, MTT assay and flow cytometry. Results showed that the HDAC2 expression was up-regulated in CRC tissues (P<0.05). HDAC2 knockdown significantly decreased cell viability at day 3 (P<0.05), day 4 (P<0.01), and day 5 (P<0.001) after infection. Then, miR-455 was verified to directly target HDAC2, resulting in a significant difference in luciferase activity (P<0.01). Moreover, miR-455 decreased the expression of HDAC2 (P<0.01). miR-455 remarkably decreased cell viability at day 3 (P<0.05), day 4 (P<0.01), and day 5 (P<0.001) after transfection while inducing cell apoptosis (P<0.001). In conclusion, miR-455 inhibited cell proliferation while inducing cell apoptosis by targeting HDAC2 in CRC cells.
