miR-708-3p promotes gastric cancer progression through downregulating ETNK1.

MicroRNAs (miRNAs) are small, evolutionarily conserved, non-coding RNAs playing a role in the proliferation, metastasis, apoptosis, chemo-sensitivity, and chemo-resistance of gastric cancer, as well as the stemness of gastric cancer stem cells. miR-708-3p induces gastric cancer cell chemo-resistance, but its actual role in gastric cancer progression remains unclear. This paper shows that miR-708-3p is upregulated in gastric cancer samples and that a high miR-708-3p expression in gastric cancer patients is associated with poor overall survival. Our functional study results indicate that miR-708-3p overexpression promotes gastric cancer cell proliferation and migration, inhibits cell apoptosis, and facilitates the transition from the G0/G1 to the G2/M phase. Furthermore, reducing miR-708-3p levels yielded opposite effects. Next, our in vivo experiments revealed that miR-708-3p advanced gastric cancer cell growth in nude mice. The underlying mechanism was the regulation of ethanolamine kinase 1 (ETNK1) expression by miR-708-3p, which bound to the 3'UTR of the ETNK1 gene in gastric cancer cells. Finally, the recovery assay results showed that ETNK1 overexpression could slow miR-708-3p-induced gastric cancer progression. In conclusion, we identified a new miR-708-3p/ETNK1 pathway involved in gastric cancer progression. These results may offer new targets for gastric cancer therapy and markers for gastric cancer prognosis.

Circular RNA circ_0000592 elevates ANXA4 expression via sponging miR-1179 to facilitate tumor progression in gastric cancer.

Increasing evidence indicated that dysregulated circular RNAs were implicated in the progression of multiple malignancies. However, the function of circ_0000592 in gastric cancer (GC) progression and its associated mechanism remain poorly understood. Quantitative real-time PCR and Western blot assay were performed to detect RNA and protein expression. Cell proliferation, migration and invasion were analyzed by 5-Ethynyl-2'-deoxyuridine staining assay, Transwell migration assay and Transwell invasion assay, respectively. The glucose/lactate assay kit was used to assess the rates of glucose consumption and lactate production. The interaction between microRNA-1179 (miR-1179) and circ_0000592 or Annexin A4 (ANXA4) was confirmed by dual-luciferase reporter assay and RNA pull-down assay. Xenograft tumor model was established to investigate the effect of circ_0000592 on tumor growth in vivo. Circ_0000592 expression was elevated in GC tissues and cells. Circ_0000592 knockdown hampered cell proliferation, migration, invasion and glycolysis of GC cells. MiR-1179 was a direct target of circ_0000592, and circ_0000592 silencing-mediated effects in GC cells were partly reversed by the knockdown of miR-1179. MiR-1179 interacted with the 3' untranslated region (3'UTR) of ANXA4. Circ_0000592 silencing reduced ANXA4 expression partly by upregulating miR-1179 in GC cells. ANXA4 overexpression partly overturned circ_0000592 knockdown-induced effects in GC cells. Circ_0000592 depletion markedly suppressed xenograft tumor growth in vivo. Circ_0000592 contributed to GC progression through regulating miR-1179/ANXA4 axis, which provided novel potential biomarkers and therapeutic targets for GC treatment.

MicroRNA-574-3p Regulates HIF-α Isoforms Promoting Gastric Cancer Epithelial-Mesenchymal Transition via Targeting CUL2.

BACKGROUND: Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. MicroRNAs (miRNAs) have been widely validated as potential biomarkers for cancer treatment and diagnosis. AIMS: This paper intends to study the effect and specific mechanism of miR-574-3p/CUL2 axis in GC. METHODS: The miR-574-3p expression in GC tissues and cell lines was analyzed by reverse transcription polymerase chain reaction (RT-PCR). GC cell (N87) proliferation, migration and invasion were determined by the Brdu assay and Transwell assay, respectively. The tumor xenotransplantation model was established in vivo to test the effect of miR-574-3p or Cullin 2 (CUL2) on tumor growth. The relationship between miR-574-3p and CUL2 was predicated by bioinformatic analysis and verified by dual-luciferase reporter assay and RIP experiment. The expression of CUL2, hypoxia-induced transcription factor-1α (HIF-1α) as well as E-cadherin, Snail and Vimentin was monitored by western blot and immunohistochemistry. RESULTS: miR-574-3p was overexpressed in GC tissues and cells. Forced upregulation of miR-574-3p enhanced proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of GC cells (N87), while downregulation of miR-574-3p resulted in reverse effects. Additionally, miR-574-3p promoted N87 cells growth and EMT in vivo. CUL2 was negatively regulated by miR-574-3p in N87 cells, and upregulation of CUL2 repressed the malignant behaviors of N87 cells. Moreover, CUL2 directly interacted with HIF-1α and suppressed HIF-1α expression both in vitro and in vivo. CONCLUSIONS: miR-574-3p targeted CUL2 to upregulate HIF-1α, thus facilitating the progression of GC.

Effect of roux-en Y gastric bypass surgery on patients with type 2 diabetes mellitus: A protocol of systematic review and meta-analysis.

BACKGROUND: Previous studies have reported that roux-en Y gastric bypass surgery (RYGBS) can benefit patients with type 2 diabetes mellitus (T2DM). However, their conclusions are still inconsistent. Thus, this study will aim to assess the effect of RYGBS for patients with T2DM. METHODS: In this study, the electronic databases of MEDLINE, EMBASE, CENTRAL, CINAHL, AMED, and CNKI from inceptions to the present without any limitations to language and publication status. All randomized controlled trials on assessing the effect of RYGBS for patients with T2DM will be included in this study. Two independent authors will carry out study search and selection according to the previous designed inclusion and exclusion criteria. At the same time, 2 authors will independently evaluate the risk of bias assessment by Cochrane risk of bias tool. Any disagreements between 2 authors will be solved by a third author through discussion. RevMan 5.3 software will be utilized for statistical analysis. RESULTS: This study will summarize the most recent studies and will provide a deeper understanding about using the effect of RYGBS for patients with T2DM. CONCLUSIONS: The findings of this study will present the existing evidence for the effect of RYGBS for patients with T2DM. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040127.

Effect of different doses of ulinastatin on cellular immunity and hepatorenal functions in patients undergoing laparoscopic colorectalcarcinoma surgery.

The effect of different doses of ulinastatin on cellular immunity and hepatorenal functions in patients undergoing laparoscopic colorectal-carcinoma surgery was observed and analyzed. The 200 patients with laparoscopic colorectal-carcinoma surgery in our hospital were selected as research subjects and divided into 4 groups containing equal patients, namely, saline group, 0.5 x 104U/kg ulinastatin group, 1 x 104U/kg ulinastatin group, and 1.5 x 104U/kg ulinastatin group, which were denoted as group A, group B, group C and group D, respectively. The treatment effect of patients in 4groups was observed and compared. By observing the Narcotrend cerebral state index (NT index), the results showed that NT index at tracheal intubation, pneumoperitoneum beginning, pneumoperitoneum 30min, resection of tumor, end of operation in 4 groups was significantly lower than that at preoperative anesthesia (T0) (p<0.05); differences in hepatorenal values (AST, ALT, BUN and Cr) among 4 groups at T0 were of no statistical significance (P>0.05); each index in T cell subsets in the postoperative third days (T1) was significantly lower than that at T0; indexes of T cell subgroup of group B, C and D at T1 were higher than that of group A at T1 (p<0.05). For 4 groups, the difference in liver and kidney function indicators at T1 and T0 was of no statistical significance, p>0.05. Different doses of ulinastatin have a certain effect on cellular immunity in patients undergoing laparoscopic colorectal-carcinoma surgery and do not significantly affect hepatorenal function.

A core cross-linked polymeric micellar platium(IV) prodrug with enhanced anticancer efficiency.

A core cross-linked polymeric micellar cisplatin(IV) conjugate prodrug is prepared by attaching the cisplatin(IV) to mPEG-b-PLL biodegradable copolymers to form micellar nanoparticles that can disintegrate to release the active anticancer agent cisplatin(II) in a mild reducing environment. Moreover, in vitro studies show that this cisplatin(IV) conjugate prodrug displays enhanced cytotoxicity against HepG2 cancer cells compared with cisplatin(II). Further studies demonstrate that the high cellular uptake and platinum-DNA adduct of this cisplatin(IV) conjugate prodrug can induce more cancer-cell apoptosis than cisplatin(II), which is responsible for its enhanced anticancer activity.