LINC01088 regulates the miR-95/LATS2 pathway through the ceRNA mechanism to inhibit the growth, invasion and migration of gastric cancer cells.

Background: In gastric cancer, a malignant condition with a dismal prognosis, long non-coding RNAs (LncRNAs) play a significant regulatory role. They often compete with microRNAs through the ceRNA mechanism to affect the expression of target mRNA. However, the specific clinical value and mechanism of action of LncRNA in gastric cancer are still unclear. Methods: This study detected the expression and clinical value of LINC01088 in gastric cancer tissues. Furthermore, the biological functions of LINC01088 and the regulation mechanism of the miR-95/LATS2 pathway were explored.Results: LINC01088 and LATS2 mRNA expression decreased, and miR-95 increased in gastric cancer tissues. LINC01088 has an excellent positive correlation with LATS2 mRNA, which may be a ceRNA pair; LINC01088 has binding sites with miR-95. Gene interference tests on gastric cancer cell lines revealed that LINC01088 could prevent gastric cancer cells from proliferating, invading, and migrating. The function of LINC01088 is achieved by regulating the miR-95/LATS2 pathway through the ceRNA mechanism.Conclusion: The results of this study show that LINC01088 expression is significantly reduced in gastric cancer tissues and cell lines. LINC01088 inhibits gastric cancer cells' proliferation, invasion, and migration by regulating the miR-95/LATS2 pathway via the ceRNA mechanism.

The Predictive Value of MAP2K1/2 Mutations on Efficiency of Immunotherapy in Melanoma.

Background: MAP2K1/2 genes are mutated in approximately 8% of melanoma patients; however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. This study focused on the correlation between MAP2K1/2 gene mutations and the treatment response. Methods: Six metastatic melanoma clinical cohorts treated with immune checkpoint inhibitors [anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) or anti-programmed cell death-1 (PD-1)] were recruited in this study. RNA expression profiling results from each of these six cohorts and the Cancer Genome Atlas (TCGA) melanoma cohort were analysed to explore the mechanism related to immune activation. Results: Compared to patients with wild-type MAP2K1/2, those with MAP2K1/2 mutations in an independent anti-CTLA-4-treated cohort had higher objective response rates, longer progression-free survival, and longer overall survival (OS). These findings were further validated in a pooled anti-CTLA-4-treated cohort in terms of the OS. However, there was no correlation between MAP2K1/2 mutations and OS in the anti-PD-1-treated cohort. Subgroup Cox regression analysis suggested that patients with MAP2K1/2 mutations received fewer benefits from anti-PD-1 monotherapy than from anti-CTLA-4 treatment. Furthermore, transcriptome profiling analysis revealed that melanoma tumours with MAP2K mutation was enriched in CD8+ T cells, B cells, and neutrophil cells, also expressed high levels of CD33 and IL10, implying a potential mechanism underlying the benefit of melanoma patients with MAP2K1/2 mutations from anti-CTLA-4 treatment. Conclusions: MAP2K1/2 mutations were identified as an independent predictive factor for anti-CTLA-4 therapy in melanoma patients. Anti-CTLA-4 treatment might be more effective than anti-PD-1 therapy for patients with MAP2K1/2-mutated melanoma.

[Preparation characterization and antitumor activity in vitro of berberine hydrochloride polymeric micelles].

With polyethylene glycol vitamin E succinate (TPGS) as the carrier materials, and berberine hydrochloride ( BER) as model drug, we formed berberine hydrochloride (BER) -loaded TPGS nanomicells (BER-PMs) using filming-rehydration method to improve its solubility and in vitro anti-tumor effect. The transmission electron microscope (TEM) was used to observe the particle appearance; particle detector was used to detect the diameter and Zeta potential; and ultracentrifugation was utilized to determine the encapsulation efficiency (EE) and drug-loading (DD); dynamic dialysis method was used to study the in vitro release behavior of BER-PMs, and the anti-tumor activity against MCF-7 cells was determined by MTT method. Results showed that the average particle size of BER-PMs was (12.45 ± 1.46) nm; particle size was uniform and spherical; drug loading and encapsulation efficiency were (5.7 ± 0.22)% and (95.67 ± 5.35)%, respectively. Zeta potential was (-1.12 ± 0.23) mV; release rate within 24 h was 37.20% and 41.14% respectively in pH 7.4 and pH 6.5 phosphate buffer in vitro; compared with BER, BER-PMs can significantly inhibit MCF-7 cell proliferation (P < 0.05), promote cell apoptosis and improve the anti-tumor activity of BER in vitro. Therefore, the formed berberine hydrochloride micelle can more effectively promote the apoptosis of MCF-7 cell, and improve the drug's in vitro anti-tumor effect.

The relationships between type 2 diabetic retinopathy and VEGF-634G/C and VEGF-460C/T polymorphisms in Han Chinese subjects.

OBJECTIVE: To investigate how VEGF-634G/C and VEGF-460C/T SNPs are related to diabetic retinopathy (DR) in Han Chinese subjects from the Shijiazhuang region of China. METHODS: Totally 376 DM cases were divided into non-proliferative diabetic retinopathy (NPDR) group (n=124), proliferative diabetic retinopathy (PDR) group (n=108), and diabetes without retinopathy (DWR) group (n=144). PCR/LDRwas utilised to detect and assess the genotypes and allele distribution frequencies at the VEGF-634G/C and VEGF-460C/T loci in each group. RESULTS: The differences between NPDR, PDR and DWR groups were not significant in genotypes and allele distribution frequencies at VEGF-634G/C locus (P>0.05). But there were significant differences between NPDR and DWR groups in genotypes (P=0.013) and allele distribution frequencies (P=0.002) at VEGF-460C/T locus, at which CT+CC genotypes were associated with a reduced risk of developing NPDR. There were no significant differences in genotypes (P=0.759) or allele distribution frequencies (P=0.433) at VEGF-460C/T locus between PDR and DWR groups. CONCLUSIONS: Among Chinese Han individuals with type-2 DM, polymorphism -634G/C of the VEGF gene was not correlated with NPDR or PDR; however, polymorphism-460C/T of the VEGF gene was correlated with NPDR, and C allele was associated with lower NPDR risk than T allele.