[Effect of acupuncture and moxibustion on expression of signal transducers and activators of transcription 3 and hypoxia-inducible factor 1α in colon mucosa in ulcerative colitis mice].

OBJECTIVE: To investigate the effect of acupuncture or moxibustion of "Zusanli" (ST36) and "Guanyuan" (CV4) on expression of signal transducers and activators of transcription 3 (STAT3) and hypoxia-inducible factor 1α (HIF-1α) in colonic tissue in ulcerative colitis (UC) mice. METHODS: Thirty-two male Kunming mice were randomly divided into control, model, acupuncture and moxibustion groups (n=8 in each group). The UC model was induced by free drinking of 3% Dextran Sodium Sulfate for 7 days. Acupuncture or moxibustion was applied to ST36 or CV4 for 15 min, once daily for 5 days. The severity of UC was monitored using the disease activity index (DAI) which includes evaluation of weight loss, stool consistency, and presence of fecal blood. Histopathological changes of the colon mucosa were observed by H.E. staining. Immunohistochemistry and Western blot were employed to detect the expression of STAT3 and HIF-1α proteins in the colon mucosa tissue. RESULTS: After modeling, the DAI, immunoactivity and expression of STAT3 and HIF-1α in the colonic tissue were significantly increased in the model group relevant to the control group (P<0.01,P<0.05). Compared with the model group, the levels of DAI, STAT3 and HIF-1α considerably decreased in both acupuncture and moxibustion groups (P<0.05), and without significant differences between the two intervention groups in the levels of DAI, STAT3 and HIF-1α after the intervention (P>0.05). H.E. staining of the colonic tissue showed damage and infiltration of inflammatory cells in the model group, and reduction of the submucosal edema and infiltrated inflammatory cells in the acupuncture and moxibustion groups. CONCLUSION: Both acupuncture and moxibustion can improve UC in UC mice, which may be associated with its effects in down-regulating the expression of colonic STAT3 and HIF-1α proteins.

LINC01554-Mediated Glucose Metabolism Reprogramming Suppresses Tumorigenicity in Hepatocellular Carcinoma via Downregulating PKM2 Expression and Inhibiting Akt/mTOR Signaling Pathway.

Background and Aims: Cancer cells prefer aerobic glycolysis to maintain growth advantages, but the role of long non-coding RNAs (lncRNAs) in glycometabolism still remains unclear. Here we identified one cytoplasmic lncRNA LINC01554 as a significantly downregulated lncRNA in hepatocellular carcinoma (HCC) and aimed to investigate its role in cellular glucose metabolism in the development and progression of HCC. Methods: Quantitative real-time PCR was used to determine the expression level of LINC01554. Downregulation of LINC01554 by miR-365a at transcriptional level was assessed by luciferase reporter assay. Subcellular fractionation assay and RNA fluorescence in situ hybridization were performed to detect the subcellular localization of LINC01554. RNA pull-down assay, mass spectrometry, and RNA immunoprecipitation assay were used to identify the underlying molecular mechanisms. The tumor-suppressive function of LINC01554 was determined by both in vitro assay and nude mice xenograft model. Results: LINC01554 was frequently downregulated in HCC, which was significantly associated with tumor invasion (P = 0.005), tumor size (P = 0.041), tumor staging (P = 0.023) and shorter survival (P = 0.035) of HCC patients. Luciferase reporter assay unraveled that LINC01554 was negatively regulated by miR-365a. Subcellular fractionation assay and RNA FISH revealed the cytoplasmic predominance of LINC01554 in MIHA cells and HCC clinical samples. Ectopic expression of LINC01554 inhibited HCC cell growth, colony formation in soft agar, foci formation, and tumor formation in nude mice. LINC01554 promoted the ubiquitin-mediated degradation of PKM2 and inhibited Akt/mTOR signaling pathway to abolish aerobic glycolysis in HCC cells. Further study found that LINC01554-knockout could effectively reverse the tumor-suppressive effect of LINC01554. Conclusions: Our results identify LINC01554 as a novel tumor suppressor in HCC and unravel its underlying molecular mechanism in reprogramming cellular glucose metabolism. LINC01554 could possibly serve as a novel prognostic biomarker and provide the rationale for HCC therapy.