LncRNA NEAT1 suppresses cellular senescence in hepatocellular carcinoma via KIF11-dependent repression of CDKN2A.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Therapeutic options for advanced HCC are limited, which is due to a lack of full understanding of pathogenesis. Cellular senescence is a state of cell cycle arrest, which plays important roles in the pathogenesis of HCC. Mechanisms underlying hepatocellular senescence are not fully understood. LncRNA NEAT1 acts as an oncogene and contributes to the development of HCC. Whether NEAT1 modulates hepatocellular senescence in HCC is unknown. METHODS: The role of NEAT1 and KIF11 in cellular senescence and tumor growth in HCC was assessed both in vitro and in vivo. RNA pulldown, mass spectrometry, Chromatin immunoprecipitation (ChIP), luciferase reporter assays, RNA FISH and immunofluorescence (IF) staining were used to explore the detailed molecular mechanism of NEAT1 and KIF11 in cellular senescence of HCC. RESULTS: We found that NEAT1 was upregulated in tumor tissues and hepatoma cells, which negatively correlated with a senescence biomarker CDKN2A encoding p16INK4a and p14ARF proteins. NEAT1 was reduced in senescent hepatoma cells induced by doxorubicin (DOXO) or serum starvation. Furthermore, NEAT1 deficiency caused senescence in cultured hepatoma cells, and protected against the progression of HCC in a mouse model. During senescence, NEAT1 translocated into cytosol and interacted with a motor protein KIF11, resulting in KIF11 protein degradation and subsequent increased expression of CDKN2A in cultured hepatoma cells. Furthermore, KIF11 knockdown caused senescence in cultured hepatoma cells. Genetic deletion of Kif11 in hepatocytes inhibited the development of HCC in a mouse model. CONCLUSIONS: Conclusively, NEAT1 overexpression reduces senescence and promotes tumor progression in HCC tissues and hepatoma cells, whereas NEAT1 deficiency causes senescence and inhibits tumor progression in HCC. This is associated with KIF11-dependent repression of CDKN2A. These findings lay the foundation to develop potential therapies for HCC by inhibiting NEAT1 and KIF11 or inducing senescence.

MUC13 promotes intrahepatic cholangiocarcinoma progression via EGFR/PI3K/AKT pathways.

BACKGROUND & AIMS: Mucin 13 (MUC13) is reportedly overexpressed in human malignancies. However, the clinicopathological and biological significance of MUC13 in human intrahepatic cholangiocarcinoma (iCCA) remain unclear. The aim of this study was to define the role of MUC13 in the progression of iCCA. METHODS: Expression levels of MUC13 in human iCCA samples were evaluated by immunohistochemistry, western blot, and real-time PCR. In vitro and in vivo experiments were used to assess the effect of MUC13 on iCCA cell growth and metastasis. Crosstalk between MUC13 and EGFR/PI3K/AKT signaling was analyzed by molecular methods. The upstream regulatory effects of MUC13 were evaluated by Luciferase and DNA methylation assays. RESULTS: MUC13 was overexpressed in human iCCA specimens and iCCA cells. MUC13 overexpression positively correlated with clinicopathological characteristics of iCCA, such as vascular invasion and lymph node metastasis, and was independently associated with poor survival. Results from loss-of-function and gain-of-function experiments suggested that knockdown of MUC13 attenuated, while overexpression of MUC13 enhanced, the proliferation, motility, and invasiveness of iCCA cells in vitro and in vivo. Mechanistically, we found that the phosphatidylinositol 3-kinase-AKT signal pathway and its downstream effectors, such as tissue inhibitor of metalloproteinases 1 and matrix metallopeptidase 9, were required for MUC13-mediated tumor metastasis of iCCA. MUC13 interacted with epidermal growth factor receptor (EGFR) and subsequently activated the EGFR/PI3K/AKT signaling pathway by promoting EGFR dimerization and preventing EGFR internalization. We also found that MUC13 was directly regulated by miR-212-3p, whose downregulation was related to aberrant CpG hypermethylation in the promoter area. CONCLUSIONS: These findings suggest that aberrant hypermethylation-induced downregulation of miR-212-3p results in overexpression of MUC13 in iCCA, leading to metastasis via activation of the EGFR/PI3K/AKT signaling pathway. LAY SUMMARY: Mucin 13 overexpression has been implicated in the development of malignancies, although its role in intrahepatic cholangiocarcinoma has not been studied. Herein, we show that mucin 13 plays a critical role in intrahepatic cholangiocarcinoma. Mucin 13 could have therapeutic value both as a prognostic marker and as a treatment target.

Therapeutic Observation of Fire Needling plus Chinese Herbal Medicine for Alopecia Areata / 上海针灸杂志

Objective To observe the clinical efficacy of fire needling plus Chinese herbal medicine in treating alopecia areata. Method Fifty patients with alopecia areata were randomized into a treatment group of 35 cases and a control group of 15 cases. The treatment group was intervened by fire needling plus Chinese herbal medicine, while the control group was by oral administration of Chinese herbal medicine alone. The clinical efficacies were compared after 3-month treatment.Result The total effective rate was 97.1% in the treatment group versus 73.3% in the control group, and the difference was statistically significant (P<0.05).Conclusion Fire needling plus Chinese herbal medicine is an effective method in treating alopecia areata.

The clinical treatment of tracheoesophageal fistula by coated stent in trachea / 中华实用儿科临床杂志

Tracheoesophageal fistula is divided into congenital and acquired tracheoesophageal fistula in the children.The main treatment is surgery,but recurrent tracheoesophageal fistula and acquired tracheoesophageal fistula caused by corrosive substance are not suitable for surgery in the short term.Endoscopic interventional therapy has become a new way of treatment,closure of tracheoesophageal fistula using a coated stent in the trachea can win time for surgical treatment and the fistula may reach the natural healing.It is an effective way of treatment.

Effect of Acupuncture on the Expression of NOS in Gastrointestinal Tissues after Abdominal Operation in Rats / 上海针灸杂志

Objective To observe the effect of acupuncture on the expression of nitricoxide synthase (NOS) in gastrointestinal tissues after operation for incomplete intestinal obstruction in rats, and to explore the mechanism of acupuncture in promoting the recovery of gastrointestinal motility. Methods Forty Sprague-Dawley (SD) rats were randomized into treatment group 1, treatment group 2, model group 1, model group 2, and a normal control group, 8 rats in each group. The incomplete intestinal obstruction models were developed by using single ligation method in treatment groups and model groups. Afterwards, the treatment groups were intervened by acupuncture at Zusanli (ST 36) and Yanglingquan (GB 34), and rats in treatment group 1 and 2 were respectively dissected after 1-day and 2-day treatment. The rats in model group 1 and 2 were respectively dissected 1 d and 2 d after modeling. The morphological observation was performed on rat’s intestinal tissues, and the average diameter of the upper part of the obstructed intestine and the expression of NOS in gastrointestinal tissues were compared. Results The average ileocecal diameter after modeling was significantly different from that in the normal control group (P0.05). The NOS content in model groups was significantly different from that in the normal group (P0.05). Conclusions Acupuncture can promote the recovery of gastrointestinal motility by regulating intestinal NOS content in rats after operation for incomplete intestinal obstruction.

Clinical Study of the Time-effect Relationship between Acupuncture and the Absorption of Cerebral Hematoma and Edema in the Acute Stage of Cerebral Hemorrhage / 上海针灸杂志

Objective To observe the time-effect relationship between acupuncture treatment and the absorption of cerebral hematoma and edema in the acute stage of cerebral hemorrhage to determine the optimal time for acupuncture intervention in cerebral hemorrhage.Methods Three hundred patients with cerebral hemorrhage in the acute stage were randomly allocated to treatment groups 1, 2, 3 and 4, and control group, 60 cases each. The control group received symptomatic treatment for regulating blood pressure, reducing intracranial pressure by dehydration, maintaining electrolyte balance, nourishing nerves and preventing and treating complications. The treatment groups were given acupuncture in addition. Treatment group 1 received acupuncture at 24 hrs after the attack; treatment group 2, at 72 hrs; treatment group 3, at one week; treatment group 4, at two weeks. Pre-/post-treatment hematoma size parameter difference value and cerebral peripheral edema grade parameters were observed in every group.Results There were statistically significant pre-/post-treatment differences in hematoma size and cerebral edema grade in every group (P<0.01,P<0.05). There were statistically significant post-treatment differences in hematoma size and cerebral edema grade between every treatment group and the control group (P<0.05). There were statistically significant post-treatment differences in hematoma size and cerebral edema grade between treatment group 1, 2 or 3 and treatment group 4 (P<0.05), between treatment group 1 or 2 and treatment group 3 (P<0.05) and between treatment groups 1 and 2 (P<0.05).Conclusions Acupuncture has a positive therapeutic effect in patients with cerebral hemorrhage in the acute stage. The earlier acupuncture intervention in the acute stage of cerebral hemorrhage, the more remarkable the effect.