BackgroundGliomas are one of the most lethal cancers in the human central nervous system. Despite clinical treatment advancements, the prognosis of patients with glioma remains poor. KDM2B is a histone lysine demethylase, which has been observed in multiple tumors. But the concrete role of KDM2B in gliomas remains to be further illustrated.MethodsThe KDM2B expression in gliomas was detected with immunohistochemistry and Western blot assay. Furthermore, knockdown of KDM2B in U87 and U251 glioma cell lines, the proliferation capacity was evaluated by cell viability assay, colon formation assay and flow cytometry in vitro. Western blot assay was used to analyze the p21, EZH2 and cyclinD1 changes followed by knockdown of KDM2B.ResultsKDM2B was upregulated in tissues of glioma patients, and the expression was correlated to cancer progression. Downregulation of KDM2B in U87 and U251 glioma cell lines inhibited cell proliferation and arrested cell cycle in G0/G1 phase. In addition, silencing KDM2B promoted the upregulation of p21 while reduced the expression of EZH2 and cyclinD1.ConclusionTaken together, our results revealed that KDM2B might influence gliomas growth and act as a novel therapeutic target for glioma patients.

S100A12 belongs to the S100 family and acts as a vital regulator in different types of tumors. However, the function of S100A12 in thyroid carcinoma has not yet been investigated. In this study, we analyzed the expression of S100A12 in human papillary thyroid cancer (PTC) samples and two PTC cell lines. In addition, we explored the effects of S100A12 on PTC cell progression in vitro and in vivo. Our results showed that S100A12 was significantly upregulated in PTC specimens. Moreover, silencing S100A12 markedly inhibited PTC cell proliferation, migration, invasion and cell cycle progression. In addition, knockdown of S100A12 significantly reduced the expression of CyclinD1, CDK4 and pERK in PTC cells. An in vivo study also showed that silencing S100A12 dramatically suppressed tumor cell growth and decreased Ki67 expression in a xenograft mouse model. This study provides novel evidence that S100A12 serves as an oncogene in PTC. Knockdown of S100A12 suppressed PTC cell proliferation, migration, and invasion and induced G0/G1 phase arrest via the inhibition of the ERK signaling pathway. Therefore, S100A12 may be a potent therapeutic target for PTC.

Individuals with TRPC6 mutations have variable phenotypes, ranging from healthy carrier to focal segmental glomerulosclerosis (FSGS) leading to renal failure. Here, we describe a family where six members had a novel TRPC6 p.R68W (c.202C>T) mutation, two of whom had renal failure from FSGS, and one had proteinuria. One healthy carrier donated a kidney to her sister. Both donor and recipient had no proteinuria at 20 years posttransplant. Two synonymous NPHS1 polymorphisms, rs2285450 (c.294C>T) and rs437168 (c.2289C>T) segregated with renal failure in this family. These variants had higher allele frequencies in 97 unrelated patients with nephrotic syndrome or FSGS compared to 224 controls. Using patch‐clamp experiments in HEK293 and podocytes, we showed that the p.R68W mutation increased TRPC6 current amplitudes, which may be explained by enhanced TRPC6 surface expression. Additionally, while wild‐type nephrin suppressed TRPC6 currents, this ability was lost in the presence of NPHS1 c.294C>T polymorphism. When cells were transfected according to combined TRPC6 and NPHS1 genotypes in the family, those representing the donor had lower TRPC6 currents than cells representing the recipient, suggesting that interactions between TRPC6 and NPHS1 variants could possibly account for the variable penetrance of TRPC6 mutations and the absence of recurrence in the graft.

Genetic variants in glioma tumor suppressor candidate region gene 1 (GLTSCR1) and ATM serine/threonine kinase (ATM) have been associated with various cancer risks. Epidemiological studies also revealed the association of variants of GLTSCR1 and ATM genes with different brain tumors. However, little is known about the relationship between both gene polymorphisms and lung cancer risk. We conducted a Chinese hospital-based casecontrol study involving 384 lung cancer cases and 387 cancer-free controls. No significant differences in the single polymorphism (GLTSCR1 rs1035938 and ATM rs11212592) association were found in five genetic models (co-dominant, dominant, recessive, overdominant and log-additive models) (adjusted by smoking duration). Join effect of three SNPs (PPP1R13L rs1970764, CD3EAP rs967591, GLTSCR1 rs1035938) on chromosome 19q13.3 showed that the designated haplotype8 (rs 1970764-rs967591-rs1035938) [OR (95% CI)=1.60(1.11-2.32), P/0.012] andhaplotype8 (rs1970764-rs967591-rs1035938) [OR (95% CI)=2.45 (1.17-5.12), P=0.018] were associated with increased risk of lung cancer (adjusted by smoking duration). The analysis of multifactor dimensionality reduction revealed that two 3-way models were the best fit models in analyses of 2 loci (P<0.001) or 4 loci (Р=0.015-0.016). The entropy-based analysis indicated the strongest synergistic effect between PPP1R13L rs1970764 and ATM rs11212592 in analysis of four genes. In conclusion, our study suggests that haplotypes consisting of PPP1R13L rs1970764-CD3EAP rs961591-GLTSCR1 rs1035938 on Chr19q13.3, interaction of smoking and GLTSCR1 rs1035938-ATM rs11212592, and synergistic action of PPP1R13L rs1970764 and ATM rs11212592 may associate with lung cancer risk in the Chinese population.

Background: Lung cancer is a complex disease that diagnosed the most common cancer and led cause of cancer death. MDM2 (MDM2 proto-oncogene) encodes a nuclear-localized E3 ubiquitin ligase. The encoded protein can promote tumor formation by targeting tumor suppressor proteins, such as TP53, for proteasomal degradation. Epidemiology studies have investigated the association of MDM2 single nucleotide polymorphisms (SNP) and interaction between genetic and environmental factors with lung cancer.Methods: This Chinese case-control study comprised 627 cases and 633 controls explored the role of MDM2 five htSNPs (rs1690924, rs1846402, rs2291857, rs3730581 and rs3730635, haplotype-tagging SNP) tagging 95% of the common haplotypes across the gene and the interactions of MDM2, PPP1R13L, CD3EAP and TP53 in the same pathological pathway on lung cancer risk, together with smoking-duration.Results: None of the htSNPs in MDM2 were associated with lung cancer risk in co-dominant, dominant, recessive, and log-additive models (adjusted for smoking-duration). Haplotype analysis showed that global haplotype association was statistically significant (P=0.0036, adjusted for smoking-duration) and haplotype5 (rs1690924 A -rs1846402 G -rs2291857 C -rs3730581 G -rs3730635 A ) was associated with reduced risk of lung cancer [OR (95%) =0.52 (0.33-0.82), P=0.0053, adjusted for smoking-duration]. MDR interaction analysis showed that two the best significant models and strong synergy between MDM2 and TP53.Conclusions: MDM2 five-htSNPs haplotype exhibited association with lung cancer susceptibility, interaction of MDM2 and TP53 htSNPs and smoking-duration contributed to lung cancer risk and strong synergy between MDM2 and TP53 htSNPs influenced lung cancer predisposition. Our results suggest that MDM2, TP53 and smoking-duration interact in relation to lung carcinogenesis.