METTL3-Mediated LINC00475 Alternative Splicing Promotes Glioma Progression by Inducing Mitochondrial Fission.

Mitochondrial fission promotes glioma progression. The function and regulation mechanisms of lncRNAs in glioma mitochondrial fission are unclear. The expression of LINC00475 and its correlation with clinical parameters in glioma were analyzed using bioinformatics. Then, in vitro and in vivo assays were performed to explore the function of spliced variant LINC00475 (LINC00475-S) in gliomas. To explore the mechanisms, RNA-seq, MeRIP, RIP, pulldown-IP, dCas9-ALKBH5 editing system, LC/MS, and Western blotting were utilized. LINC00475 was confirmed to be overexpressed and with higher frequencies of AS events in gliomas compared to normal brain tissue and was associated with worse prognosis. In vitro and animal tumor formation experiments demonstrated that the effect of LINC00475-S on proliferation, metastasis, autophagy, and mitochondrial fission of glioma cells was significantly stronger than that of LINC00475. Mechanistically, METTL3 induced the generation of LINC00475-S by splicing LINC00475 through m6A modification and subsequently promotes mitochondrial fission in glioma cells by inhibiting the expression of MIF. Pull-down combined LC/MS and RIP assays identified that the m6A recognition protein HNRNPH1 bound to LINC00475 within GYR and GY domains and promoted LINC00475 splicing. METTL3 facilitated HNRNPH1 binding to LINC00475 in an m6A-dependent manner, thereby inducing generation of LINC00475-S. METTL3 facilitated HNRNPH1-mediated AS of LINC00475, which promoted glioma progression by inducing mitochondrial fission. Targeting AS of LINC00475 and m6A editing could serve as a therapeutic strategy against gliomas.

Association of LINC00673 rs11655237 polymorphism with pediatric glioma susceptibility in a Chinese population.

BACKGROUND: Previous researches have suggested that LINC00673 rs11655237 C>T polymorphism might be correlated to cancer susceptibility. However, its correlation with pediatric glioma is unknown. Therefore, this study aimed to determine whether LINC00673 rs11655237 C>T polymorphism is correlated with pediatric glioma. METHODS: In total, we included 399 subjects from South China. The Student's t-test was performed to evaluate age differences between glioma cases and controls. Differences in the categorical variables between the two groups were assessed using the χ2 test. A logistic regression was conducted to calculate the odds ratio (OR) and the 95% confidence interval (CI). RESULTS: We conducted this case-control study to investigate the association between LINC00673 polymorphism and pediatric glioma susceptibility. Our results revealed that LINC00673 rs11655237 C>T polymorphism was not correlated to pediatric glioma susceptibility in a Chinese population (CC/CT compared with TT: adjusted OR =2.49, 95% CI: 0.87-7.15, P=0.091). Furthermore, a stratified analysis also indicated LINC00673 rs11655237 C>T polymorphism did not increase the risk of glioma in different subgroups. CONCLUSIONS: Our study revealed that LINC00673 rs11655237 C>T polymorphism was not correlated to pediatric glioma susceptibility in a Chinese population. In the future, further exploration of this genetic factor in relation to glioma susceptibility will require a larger sample size to verify the current findings.

The correlation between polymorphisms in the XPC gene and glioma susceptibility in a Chinese pediatric population.

BACKGROUND: A previous study revealed that single nucleotide polymorphisms (SNPs) in coding genes play a key role in tumorigenesis, genetic disorders, and drug resistance. Xeroderma pigmentosum group C (XPC) protein is a key DNA damage recognition factor that is required for maintaining the genomic stability. However, the correlation between XPC polymorphisms and glioma susceptibility is still unclear. Hence, this study aimed to investigate the correlation between XPC polymorphisms and pediatric glioma susceptibility. METHODS: A total of 399 participants (171 glioma patients and 228 controls) were enrolled to evaluate the correlation between XPC polymorphism and pediatric glioma susceptibility. The count data of two groups was analyzed by chi-squared (χ2) test. Moreover, logistic regression was used to assess the strength of XPC polymorphisms associated with glioma susceptibility. RESULTS: We identified that XPC rs1870134 G>C reduced pediatric glioma susceptibility. Compared to participants with rs1870134 GG/GC genotypes, those with rs1870134 CC genotype had a significantly lower risk for glioma [adjusted odds ratio (AOR) =0.10, 95% confidence interval (CI): 0.01 to 0.78, P=0.028]. Patients with 4-5 genotypes have higher risk of glioma than those with 0-3 genotypes (AOR =1.59, 95% CI: 1.04 to 2.43, P=0.031). The stratified analysis showed that the risky effects of rs2228000 CT/TT genotypes and rs2229090 GC/CC genotypes were more predominant among children aged ≥60 months, astrocytic tumors, and clinical stage I. CONCLUSIONS: We found for the first time that XPC polymorphisms had a statistically significant correlation with pediatric glioma susceptibility in a Chinese population. The XPC rs2228000 CT/TT and rs2229090 GC/CC genotypes could both increase the risk of pediatric glioma in subgroups with females, astrocytic tumors, and clinical stage I. The XPC polymorphism has potential to be a useful adjunct method to screen pediatric glioma.

Effect of production temperature and particle size of rice husk biochar on mercury immobilization and erosion prevention of a mercury contaminated soil.

Mercury (Hg) contaminated soil is a potential hazardous material especially under soil erosion and surface runoff. This work aims to use rice husk biochar to immobilize Hg and prevent erosion, and find the optimal production temperature and particle size of the biochar. The biochars were produced at 300, 500, and 700 °C and sieved to three particle sizes ~20, < 2, and < 0.15 mm. They were applied to a Hg contaminated loamy sand (20.2 mg/kg) and undergone simulated rainfall erosion representing 7 years of heavy rain events in Beijing. All biochar amendments reduced the runoff volume by 5.1-15.4%. Hg amount in runoff were significantly reduced by 36.7-48.8% after the amendments of biochar. The Hg concentration of infiltration was reduced by biochar treatments except that produced at 300 °C, while its amount was increased due to larger infiltration volume. All biochar amendments significantly reduced soil loss in runoff by 43.5-77.2%. Hg was enriched in the sediments (39.7-46.8 mg/kg) compared with the parent soil (20.2 mg/kg) regardless of biochar treatment, but its bioavailability was low. Higher pyrolysis temperature of the rice husk biochars resulted in less runoff, more infiltration, and better erosion prevention, while the effect of biochar particle size is less significant.

Temporal effect of MgO reactivity on the stabilization of lead contaminated soil.

Elevated soil lead (Pb) concentrations are a global concern owing to the toxic effects of this heavy metal. Solidification/stabilization (S/S) of soils using reagents like Portland cement (PC) is a common approach for the remediation of Pb contaminated sites. However, it has been reported that under long-term field conditions, the performance of PC treatments can diminish significantly. Therefore, novel reagents that provide longer-term stabilization performance are needed. In this study, four magnesium oxide (MgO) products of different reactivity values were applied (5 wt%) to a Pb contaminated clayey soil. The short-term (1-49 days) and long-term (25-100 years) temporal stabilization effects were investigated by laboratory incubation and accelerated ageing methods, respectively. The concentration of Pb in Toxicity Characterization Leaching Procure (TCLP) leachate was ~14 mg/L for the untreated soil; ~1.8 times higher than the TCLP regulatory level (5 mg/L). Only one day after treatment with MgO, the leachate concentration was reduced to below the regulatory level (a reduction of 69.4%-83.2%), regardless of the MgO type applied. However, in the long-term accelerated ageing experiments, only treatments using the most reactive MgO type could provide leachate concentrations that were consistently below the TCLP threshold throughout the 100 years of simulated ageing. The soil treated with the MgO of lowest reactivity was the first to exceed the regulatory level, at simulated year 75. It is thus demonstrated that MgO reactivity has a significant effect on its long-term effectiveness for contaminated soil stabilization. This is attributed to differences in their specific surface area and readiness to carbonate, which may facilitate the immobilization of Pb in the long term. It is also noteworthy that compared to PC, reactive MgO is more environmentally friendly owing to lower energy consumption and reduced CO2 emissions during its manufacture.

The rs2147578 C > G polymorphism in the Inc-LAMC2-1:1 gene is associated with increased neuroblastoma risk in the Henan children.

BACKGROUND: The rs2147578 C > G polymorphism in the long non-coding RNA gene Lnc-LAMC2-1:1 is associated with increased susceptibility to a few types of cancers. However, its role in neuroblastoma has not been evaluated yet. METHODS: We investigated the association between the lnc-LAMC2-1:1 rs2147578 C > G polymorphism and neuroblastoma susceptibility in Chinese Han populations. A total of 393 neuroblastoma cases and 812 healthy individuals from the Henan and Guangdong provinces were enrolled and subjected to genotyping. Odds ratio (OR) and 95% confidence interval (CI) were used to determine the strength of the association of interest. RESULTS: Combined analysis revealed that the lnc-LAMC2-1:1 rs2147578 C > G polymorphism was associated with increased neuroblastoma susceptibility (CG vs. CC: adjusted OR = 1.33, 95% CI = 1.01-1.75, P = 0.045; CG/GG vs. CC: adjusted OR = 1.34, 95% CI = 1.03-1.74, P = 0.028). In stratification analysis, children under 18 months with rs2147578 CG/GG genotypes had an increased neuroblastoma risk (adjusted OR = 1.70, 95% CI = 1.08-2.67, P = 0.022). Females with rs2147578 CG/GG genotypes also had increased neuroblastoma susceptibility (adjusted OR = 2.08, 95% CI = 1.37-3.18, P = 0.0007). In addition, children with lnc-LAMC2-1:1 rs2147578 CG/GG genotypes were prone to develop earlier stages of neuroblastoma (adjusted OR = 1.46, 95% CI = 1.01-2.12, P = 0.046). CONCLUSIONS: The Lnc-LAMC2-1:1 rs2147578 C > G polymorphism may contribute to increased neuroblastoma susceptibility in children of Henan province.

LINC00673 rs11655237 C>T confers neuroblastoma susceptibility in Chinese population.

Neuroblastoma, which accounts for approximately 10% of all pediatric cancer-related deaths, has become a therapeutic challenge and global burden attributed to poor outcomes and mortality rates of its high-risk form. Previous genome-wide association studies (GWASs) identified the LINC00673 rs11655237 C>T polymorphism to be associated with the susceptibility of several malignant tumors. However, the association between this polymorphism and neuroblastoma susceptibility is not clear. We genotyped LINC00673 rs11655237 C>T in 393 neuroblastoma patients in comparison with 812 age-, gender-, and ethnicity-matched healthy controls. We found a significant association between the LINC00673 rs11655237 C>T polymorphism and neuroblastoma risk (TT compared with CC: adjusted odds ratio (OR) =1.80, 95% confidence interval (CI) =1.06-3.06, P=0.029; TT/CT compared with CC: adjusted OR =1.31, 95% CI =1.02-1.67, P=0.033; and T compared with C: adjusted OR =1.29, 95% CI =1.06-1.58, P=0.013). Furthermore, stratified analysis indicated that the rs11655237 T allele carriers were associated with increased neuroblastoma risk for patients with tumor originating from the adrenal gland (adjusted OR =1.51, 95% CI =1.06-2.14, P=0.021) and International Neuroblastoma Staging System (INSS) stage IV disease (adjusted OR =1.60, 95% CI =1.12-2.30, P=0.011). In conclusion, we verified that the LINC00673 rs11655237 C>T polymorphism might be associated with neuroblastoma susceptibility. Prospective studies with a large sample size and different ethnicities are needed to validate our findings.

HSD17B12 gene rs11037575 C>T polymorphism confers neuroblastoma susceptibility in a Southern Chinese population.

A previous genome-wide association study (GWAS) identified four genetic polymorphisms (rs1027702 near DUSP12, rs10055201 in IL31RA, rs2619046 in DDX4, and rs11037575 in HSD17B12 gene) that were associated with neuroblastoma susceptibility, especially for low-risk subjects. The aim of this study was to examine the association between these four polymorphisms and neuroblastoma susceptibility in a Southern Chinese population composed of 256 cases and 531 controls. Overall, among all the polymorphisms, single-locus analysis only revealed significant association between the HSD17B12 rs11037575 C>T polymorphism and neuroblastoma susceptibility (CT vs CC: adjusted odds ratio [OR] =0.71, 95% confidence interval [CI] =0.51-0.97, P=0.030). Moreover, stratified analysis indicated that the rs11037575 T allele was associated with decreased neuroblastoma risk among the children aged 0-18 months (adjusted OR =0.60, 95% CI =0.37-0.97, P=0.036); regarding the tumor site, this polymorphism protected against tumor in the mediastinum (adjusted OR =0.59, 95% CI =0.37-0.94, P=0.025). When risk genotypes were combined, we found that girls with two to four risk genotypes were at a significantly increased risk of neuroblastoma (adjusted OR =1.65, 95% CI =1.03-2.64, P=0.039). In terms of clinical stages, individuals with two to four risk genotypes had a tendency toward the development of stage III/IV diseases (adjusted OR =1.69, 95% CI =1.12-2.54, P=0.012). In conclusion, we verified that the HSD17B12 rs11037575 T allele might negatively associate with neuroblastoma risk. These findings need further validation by prospective studies with larger sample size and different ethnicities.

The TP53 gene rs1042522 C>G polymorphism and neuroblastoma risk in Chinese children.

TP53, a tumor suppressor gene, plays a critical role in cell cycle control, apoptosis, and DNA damage repair. Previous studies have indicated that the TP53 gene Arg72Pro (rs1042522 C>G) polymorphism is associated with susceptibility to various types of cancer. We evaluated the association of the TP53 gene rs1042522 C>G polymorphism with neuroblastoma susceptibility in a hospital-based study among the Chinese Han population. Enrolled were 256 patients and 531 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) generated using logistic regression models were used to determine the strength of the association of interest. No association was detected between rs1042522 C>G polymorphism and neuroblastoma risk. In our stratification analysis of age, gender, sites of origin, and clinical stages, we observed that subjects with rs1042522 CG/GG genotypes had a lower risk of developing neuroblastoma in the mediastinum (Adjusted OR=0.52, 95% CI=0.33-0.82, P=0.005) than those carrying the CC genotype. These results indicate that TP53 gene rs1042522 C>G polymorphism may exert a weak and site-specific effect on neuroblastoma risk in Southern Chinese children and warrant further confirmation.

Common variations within HACE1 gene and neuroblastoma susceptibility in a Southern Chinese population.

Neuroblastoma is a common fatal pediatric cancer of the developing sympathetic nervous system, which accounts for ~10% of all pediatric cancer deaths. To investigate genetic risk factors related to neuroblastoma, many genome-wide association studies have been performed, and single nucleotide polymorphisms (SNPs) within HACE1 gene have been identified to associate with neuroblastoma risk. However, the association of the HACE1 SNPs with neuroblastoma needs to be validated in Southern Chinese children. We genotyped five SNPs located in the HACE1 gene (rs4336470 C>T, rs9404576 T>G, rs4079063 A>G, rs2499663 T>C, and rs2499667 A>G) in 256 Southern Chinese patients in comparison with 531 ethnically matched healthy controls. Single locus analysis showed no significant association between any of HACE1 SNPs and neuroblastoma risk in Southern Chinese children. However, when all the risk genotypes were combined, we found a borderline significant trend toward an increased neuroblastoma risk with 4-5 risk genotypes (adjusted odds ratio =1.36, 95% confidence interval =0.98-1.89, P=0.065). Moreover, stratified analysis found that carriers of 4-5 risk genotypes tended to develop neuroblastoma in the retroperitoneal region and have more aggressive tumors, progressing to advanced clinical stages III/IV, when compared with those of 0-3 risk genotypes. In conclusion, HACE1 gene may have weak effect on neuroblastoma risk in Southern Chinese children. Large well-designed studies are needed to strengthen our findings.