[Retracted] Downregulation of microRNA­198 suppresses cell proliferation and invasion in retinoblastoma by directly targeting PTEN.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the data shown for the cell invasion assays in Figs. 2C and 4C were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 18: 595­602, 2018; DOI: 10.3892/mmr.2018.8979].

Oncogenic magnesium transporter 1 upregulates programmed death-1-ligand 1 expression and contributes to growth and radioresistance of glioma cells through the ERK/MAPK signaling pathway.

Radiotherapy has been established as a major therapeutic modality for glioma, whereas new therapeutic targets are needed to prevent tumor recurrence. This study intends to explore the regulatory role of magnesium transporter 1 (MAGT1) in radiotherapy resistance of glioma through modulating ERK and programmed death-1-ligand 1 (PD-L1). Our bioinformatics analysis identified differentially expressed MAGT1 in glioma, expression of which was subsequently determined in cohort data of TCGA database and microarray dataset as well as glioma cell lines. Artificial modulation of MAGT1, ERK, and PD-L1 expression was performed to examine their effects on glioma cell proliferation and radioresistance, as reflected by MTT and colony formation assays under irradiation. Mouse glioma cells with manipulated MAGT1 and ERK inhibitors were further injected into mice to assess the in vivo tumor formation ability of glioma cells. It was noted that MAGT1 expression was highly expressed in glioma tissues of TCGA data and microarray dataset, which was then validated in glioma cell lines. Ectopic expression of MAGT1 was revealed to promote the proliferation and radioresistance of glioma cells, which was attributed to the MAGT1-mediated activation of the ERK/MAPK signaling pathway. It was illuminated that MAGT1 stimulated PD-L1 expression through the ERK/MAPK pathway and thus facilitated glioma cell growth. Additionally, MAGT1 overexpression accelerated the in vivo tumor formation of glioma cells, while the ERK inhibitor negated its effect. In conclusion, MAGT1 enhances the growth and radioresistance of glioma cells through the ERK/MAPK signaling pathway-mediated upregulation of PD-L1 expression.

A Hybrid Assembly with Nickel Poly-Pyridine Polymer on CdS Quantum Dots for Photo-Reducing CO2 into Syngas with Controlled H2 /CO Ratios.

A hybrid photocatalytic assembly with Ni poly-pyridine polymers binding on CdS quantum dots was developed via thiophene immobilization. The fabricated hybrid assembly facilitated efficient charge separation, and each component endowed great synergy. As a result, a high syngas production rate was achieved over 5500 µmol gcat -1 h-1 from photocatalytic CO2 reduction under visible-light irradiation, accompanied by an adjustable H2 /CO ratio ranging from 4 : 1 to 1 : 3. A novel hybrid assembly was described for syngas synthesis with boosted activity and controlled selectivity, which provides a profile to ingeniously understand molecular-level design for photocatalysts.

Application of gene polymorphisms to predict the sensitivity of patients with locally advanced non-small cell lung cancer undergoing chemoradiotherapy.

OBJECTIVE: To analyze the value of gene polymorphisms in predicting the sensitivity of patients with locally advanced non-small-cell lung cancer (NSCLC) undergoing chemoradiotherapy. METHODS: Patients with locally advanced NSCLC undergoing chemoradiotherapy in our hospital from February 2017 to August 2019 were enrolled. X-ray repair cross complementing group 1 (XRCC1) gene polymorphisms were detected before chemoradiotherapy, and the correlation of XRCC1 gene polymorphisms with the sensitivity was analyzed. RESULTS: There was no significant correlation of XRCC1 gene polymorphisms with age, gender, smoking status, pathological type, clinical stage and tumor size (P > 0.05). Among 98 patients with locally advanced NSCLC, 17 patients had complete response (CR), 25 patients had partial response (PR), 37 patients had stable disease (SD), and 19 patients had progressive disease (PD). A total of 42 patients were sensitive to chemoradiotherapy (CR + PR), and 56 patients were insensitive to treatment (SD + PD). The effect of XRCC1 gene polymorphisms on the efficacy of chemoradiotherapy was statistically significant (P < 0.05). In the codominant model GG vs. GA vs. AA, there was a significant difference (χ2 = 6.473, P = 0.039); The difference between AA and GA was significant (χ2 = 4.572, P = 0.032). The difference between AA and GG was significant (χ2 = 6.003, P = 0.014). There was no significant difference between GA and GG (χ2 = 0.015, P = 0.901). The rates of effective treatment for patients with XRCCI GG vs. GA vs. AA genotypes were 79.17%, 57.14%, and 47.37%, respectively. GG type was 1.38 times more effective than GA type, and GA type was 1.21 times more than AA type. CONCLUSION: The Arg399Gln polymorphism of XRCC1 gene was significantly related to the sensitivity of patients with locally advanced NSCLC undergoing chemoradiotherapy. The sensitivity of patients carrying wild-type gene AA to chemoradiotherapy was significantly better than that of patients with GA and GG.

Metallothionein-1G suppresses pancreatic cancer cell stemness by limiting activin A secretion via NF-κB inhibition.

Resistance to chemotherapy is a long-standing problem in the management of cancer, and cancer stem cells are regarded as the main source of this resistance. This study aimed to investigate metallothionein (MT)-1G involvement in the regulation of cancer stemness and provide a strategy to overcome chemoresistance in pancreatic ductal adenocarcinoma (PDAC). Methods: MT1G was identified as a critical factor related with gemcitabine resistance in PDAC cells by mRNA microarray. Its effects on PDAC stemness were evaluated through sphere formation and tumorigenicity. LC-MS/MS analysis of conditional medium revealed that activin A, a NF-κB target, was a major protein secreted from gemcitabine resistant PDAC cells. Both loss-of-function and gain-of-function approaches were used to validate that MT1G inhibited NF-κB-activin A pathway. Orthotopic pancreatic tumor model was employed to explore the effects on gemcitabine resistance with recombinant follistatin to block activin A. Results: Downregulation of MT1G due to hypermethylation of its promoter is related with pancreatic cancer stemness. Secretome analysis revealed that activin A, a NF-κB target, was highly secreted by drug resistant cells. It promotes pancreatic cancer stemness in Smad4-dependent or independent manners. Mechanistically, MT1G negatively regulates NF-κB signaling and promotes the degradation of NF-κB p65 subunit by enhancing the expression of E3 ligase TRAF7. Blockade of activin A signaling with follistatin could overcome gemcitabine resistance. Conclusions: MT1G suppresses PDAC stemness by limiting activin A secretion via NF-κB inhibition. The blockade of the activin A signaling with follistatin may provide a promising therapeutic strategy for overcoming gemcitabine resistance in PDAC.

miR-340 Exerts Suppressive Effect on Retinoblastoma Progression by Targeting KIF14.

Purpose: This work aimed to investigate the influences of microRNA-340 (miR-340) on proliferation and apoptosis of retinoblastoma (RB) cells and explore its regulatory mechanism. MATERIALS AND METHODS: miR-340 mimic and inhibitor were applied for up-regulating or inhibiting the expression of miR-340 in RB cell lines. Then, CCK-8 and AnnexinV-FITC/PI staining were used to measure cell proliferation and apoptosis, respectively. After that, luciferase assay was performed to affirm the direct targets of miR-340. Furthermore, qRT-PCR and western blotting assay were carried out to detect the levels of miR-340 and KIF14. RESULTS: Our results indicated that the miR-340 was lowly expressed in RB cell lines, and up-regulation of miR-340 can decrease the proliferation and induce the apoptosis of RB cells. Moreover, we verified that miR-340 controls KIF14 expression, either directly or through a subsequent molecular cascade, and inversely related to its expression. The results obtained from the rescue assays presented that over-expression of KIF14 reversed the miR-340-mediated inhibition on malignant phenotype of RB cells. CONCLUSIONS: Overall, we proved that miR-340 can decrease the proliferation and increase the apoptosis of RB cells, and its function in RB cells was at least partially achieved via down-regulation of KIF14, prompting that miR-340 was expected to supply a new direction for clinical therapy of RB in the future.

Diabetic retinopathy predicts cardiovascular mortality in diabetes: a meta-analysis.

BACKGROUND: The prognostic significance of diabetic retinopathy (DR) for cardiovascular diseases (CVD) remained unclear. Therefore, we performed this meta-analysis to assess whether DR predicted CVD mortality in diabetic patients. METHODS: We searched PubMed, Embase, Web of Science and Cochrane Library for cohort studies reporting the association of DR and CVD mortality. Then we pooled the data for analysis. RESULTS: After screening the literature, 10 eligible studies with 11,239 diabetic subjects were finally included in quantitative synthesis. The pooled risk ratio (RR) of DR, mild DR, and severe DR for CVD mortality was 1.83 (95% confidence interval (CI): 1.42, 2.36; p < 0.001), 1.13 (95% CI 0.81, 1.59; p = 0.46), and 2.26 (1.31, 3.91; p = 0.003), respectively, compared to those without DR. In type 2 DM, the patients with DR had a significantly higher CVD mortality (RR: 1.69; 95% CI 1.27, 2.24; p < 0.001). Subgroup analysis also showed a significantly higher CVD mortality in DR according to various regions, study design, data source, and follow-up period (all RR > 1; all P values < 0.05). Data from 2 studies showed no significant correlation of DR and CVD mortality in diabetic patients receiving cardiovascular surgery (RR: 2.40; 95% CI 0.63, 9.18; P = 0.200). CONCLUSIONS: DR is a risk marker of cardiovascular death, and severe DR predicts a doubled mortality of CVD in diabetes. These findings indicate the importance of early identification and management of diabetic patients with DR to reduce the risk of death.

Downregulation of microRNA­198 suppresses cell proliferation and invasion in retinoblastoma by directly targeting PTEN.

A number of studies have highlighted that aberrantly expressed microRNAs (miRNAs/miRs) serve crucial roles in the tumorigenesis and tumor development of retinoblastoma (RB). Hence, a full investigation of the biological roles and regulatory mechanisms of miRNAs in RB may provide novel therapeutic targets for patients with this malignancy. miR­198 is frequently abnormally expressed in various types of human cancers. However, the expression level, biological roles and underlying mechanisms of miR­198 in RB remain to be elucidated. In the present study, miR­198 expression was upregulated in RB tissues and cell lines. Silencing of miR­198 attenuated cell proliferation and invasion in RB. In addition, phosphatase and tensin homolog deleted on chromosome ten (PTEN) was predicted as a potential target of miR­198 using bioinformatics analysis. Subsequent luciferase reporter assay indicated that the 3'­untranslated region of PTEN can be directly targeted by miR­198. Furthermore, miR­198 inhibition increased the PTEN expression at the mRNA and protein levels in RB cells. In addition, PTEN mRNA expression was downregulated in RB tissues, and this downregulation was inversely associated with the expression level of miR­198. PTEN knockdown rescued the inhibitory effects of miR­198 underexpression on cell proliferation and invasion in RB. Notably, the downregulation of miR­198 inactivated the phosphoinositide 3­kinase (PI3K)/protein kinase B (AKT) signaling pathway in RB. These results demonstrated that miR­198 may serve oncogenic roles in RB by directly targeting PTEN and regulating the PI3K/AKT signaling pathway. Hence, miR­198 may be a promising therapeutic target for patients with RB.