Role of protein degradation systems in colorectal cancer.

Protein degradation is essential for maintaining protein homeostasis. The ubiquitin‒proteasome system (UPS) and autophagy-lysosome system are the two primary pathways responsible for protein degradation and directly related to cell survival. In malignant tumors, the UPS plays a critical role in managing the excessive protein load caused by cancer cells hyperproliferation. In this review, we provide a comprehensive overview of the dual roles played by the UPS and autolysosome system in colorectal cancer (CRC), elucidating their impact on the initiation and progression of this disease while also highlighting their compensatory relationship. Simultaneously targeting both protein degradation pathways offers new promise for enhancing treatment efficacy against CRC. Additionally, apoptosis is closely linked to ubiquitination and autophagy, and caspases degrade proteins. A thorough comprehension of the interplay between various protein degradation pathways is highly important for clarifying the mechanism underlying the onset and progression of CRC.

A prognostic marker LTBP1 is associated with epithelial mesenchymal transition and can promote the progression of gastric cancer.

LTBP1 is closely related to TGF-ß1 function as an essential component, which was unclear in gastric cancer (GC). Harbin Medical University (HMU)-GC cohort and The Cancer Genome Atlas (TCGA) dataset were combined to form a training cohort to calculate the connection between LTBP1 mRNA expression, prognosis and clinicopathological features. The training cohort was also used to verify the biological function of LTBP1 and its relationship with immune microenvironment and chemosensitivity. In the tissue microarrays (TMAs), immunohistochemical (IHC) staining was performed to observe LTBP1 protein expression. The correlation between LTBP1 protein expression level and prognosis was also analyzed, and a nomogram model was constructed. Western blotting (WB) was used in cell lines to assess LTBP1 expression. Transwell assays and CCK-8 were employed to assess LTBP1's biological roles. In compared to normal gastric tissues, LTBP1 expression was upregulated in GC tissues, and high expression was linked to a bad prognosis for GC patients. Based on a gene enrichment analysis, LTBP1 was primarily enriched in the TGF-ß and EMT signaling pathways. Furthermore, high expression of LTBP1 in the tumor microenvironment was positively correlated with an immunosuppressive response. We also found that LTBP1 expression (p = 0.006) and metastatic lymph node ratio (p = 0.044) were independent prognostic risk factors for GC patients. The prognostic model combining LTBP1 expression and lymph node metastasis ratio reliably predicted the prognosis of GC patients. In vitro proliferation and invasion of MKN-45 GC cells were inhibited and their viability was decreased by LTBP1 knockout. LTBP1 plays an essential role in the development and progression of GC, and is a potential prognostic biomarker and therapeutic target for GC.

Persistence of severe global inequalities in the burden of blindness and vision loss from 1990 to 2019: findings from the Global Burden of Disease Study 2019.

AIMS: To assess the global burden and economic inequalities in the distribution of blindness and vision loss between 1990 and 2019. METHODS: A secondary analysis of the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019. Data for disability-adjusted life-years (DALYs) due to blindness and vision loss were extracted from the GBD 2019. Data for gross domestic product per capita were extracted from the World Bank database. Slope index of inequality (SII) and concentration index were computed to assess absolute and relative cross-national health inequality, respectively. RESULTS: Countries with high, high-middle, middle, low-middle and low Socio-demographic Index (SDI) had decline of age-standardised DALY rate of 4.3%, 5.2%, 16.0%, 21.4% and 11.30% from 1990 to 2019, respectively. The poorest 50% of world citizens bore 59.0% and 66.2% of the burden of blindness and vision loss in 1990 and 2019, respectively. The absolute cross-national inequality (SII) fell from -303.5 (95% CI -370.8 to -236.2) in 1990 to -256.0 (95% CI -288.1 to -223.8) in 2019. The relative inequality (concentration index) for global blindness and vision loss remained essentially constant between 1991 (-0.197, 95% CI -0.234 to -0.160) and 2019 (-0.193, 95% CI -0.216 to -0.169). CONCLUSION: Though countries with middle and low-middle SDI were the most successful in decreasing burden of blindness and vision loss, a high level of cross-national health inequality persisted over the past three decades. More attention must be paid to the elimination of avoidable blindness and vision loss in low-income and middle-income countries.

Cancer-associated fibroblast expression of glutamine fructose-6-phosphate aminotransferase 2 (GFPT2) is a prognostic marker in gastric cancer.

Glutamine fructose-6-phosphate aminotransferase 2 (GFPT2) is a rate-limiting enzyme in hexosamine biosynthesis involved in the occurrence and progress of many cancers. What role it plays in gastric cancer (GC) is still unclear. In this study, transcriptome sequencing data from the Harbin Medical University (HMU)-GC cohort and The Cancer Genome Atlas (TCGA) dataset were combined with the HMU-TCGA training cohort to analyze the biological function and clinical significance of GFPT2. The correlation of GFPT2 with immune cells and stromal cells was analyzed in the GC immune microenvironment through transcriptome sequencing data and a public single-cell sequencing database. In cell lines, GC tissues, and the tissue microarray, GFPT2 protein expression was confirmed by western blotting and immunohistochemistry. The mRNA of GFPT2 was highly expressed in the tumor (p < 0.001), and GC cells and tumors expressed high levels of GFPT2 protein. Compared to low expression, high GFPT2 mRNA expression was associated with higher levels of tumor invasion, higher pathological stages, and poor prognosis (p = 0.02) in GC patients. In a drug susceptibility analysis, GFPT2 mRNA expression was associated with multiple chemotherapeutic drug sensitivity, including docetaxel, paclitaxel, and cisplatin. Gene enrichment analysis found that GFPT2 was mainly primarily involved in the extracellular matrix receptor interaction pathway. The ESTIMATE, CIBERSORT, and ssGSEA algorithms showed that GFPT2 was associated with immune cell infiltration. In addition, GFPT2 was more likely to be expressed within cancer-associated fibroblasts (CAFs), and high levels of GFPT2 expression were highly correlated with four CAFs scores (all p < 0.05). Finally, a prognostic model to assess the risk of death in GC patients was constructed based on GFPT2 protein expression and lymph node metastasis rate. In conclusion, GFPT2 plays an essential role in the function of CAFs in GC. It can be used as a biomarker to assess GC prognosis and immune infiltration.

Global, regional, and national burden of multiple sclerosis from 1990 to 2019: Findings of global burden of disease study 2019.

Background: The global rising prevalence and incidence of multiple sclerosis (MS) has been reported during the past decades. However, details regarding the evolution of MS burden have not been fully studied. This study aimed to investigate the global, regional, and national burden and temporal trends in MS incidence, deaths, and disability-adjusted life years (DALYs) from 1990 to 2019 using the age-period-cohort analysis. Methods: We performed a secondary comprehensive analysis of incidence, deaths, and DALYs of MS by calculating the estimated annual percentage change from 1990 to 2019 obtained from the Global Burden of Disease (GBD) 2019 study. The independent age, period, and birth cohort effects were evaluated by an age-period-cohort model. Results: In 2019, there were 59,345 incident MS cases and 22,439 MS deaths worldwide. The global number of incidences, deaths, and DALYs of MS followed an upward trend, whereas the age-standardized rates (ASR) slightly declined from 1990 to 2019. High socio-demographic index (SDI) regions had the highest ASR of incidences, deaths, and DALYs in 2019, while the rate of deaths and DALYs in medium SDI regions are the lowest. Six regions which include high-income North America, Western Europe, Australasia, Central Europe, and Eastern Europe had higher ASR of incidences, deaths, and DALYs than other regions in 2019. The age effect showed that the relative risks (RRs) of incidence and DALYs reached the peak at ages 30-39 and 50-59, respectively. The period effect showed that the RRs of deaths and DALYs increased with the period. The cohort effect showed that the later cohort has lower RRs of deaths and DALYs than the early cohort. Conclusion: The global cases of incidence, deaths, and DALYs of MS have all increased, whereas ASR has declined, with different trends in different regions. High SDI regions such as European countries have a substantial burden of MS. There are significant age effects for incidence, deaths, and DALYs of MS globally, and period effects and cohort effects for deaths and DALYs.

Clinical and Biological Significances of FBLN5 in Gastric Cancer.

Abnormal FBLN5 expression levels are related to various cancer types. This study is the first to explore its clinical and biological significances in gastric cancer (GC). We used The Cancer Genome Atlas-GC (TCGA-GC) and Gene Expression Omnibus (GEO) databases to identify the differential expression of FBLN5, and its association with clinical pathological characteristics was analyzed. A Kaplan-Meier plotter was used to calculate the impact of FBLN5 on GC patient prognosis, and the biological functions of FBLN5 were analyzed. In addition, we constructed a GC tissue microarray, and performed an immunohistochemical staining of FBLN5 to verify our findings. Western blotting was conducted simultaneously to confirm that FBLN5 was overexpressed in GC. We found that the high level of FBLN5 mRNA in GC was associated with a poor prognosis. High FBLN5 expression levels were significantly correlated with INFc and N3 lymph node metastasis. Univariate and multivariate analyses showed that FBLN5 expression levels and lymph node metastasis rate were independent risk factors related to GC patient prognosis, which can be combined to construct a nomogram to serve patients. Therefore, we believe that FBLN5 is significantly related to the poor prognosis of GC patients. FBLN5 is a valuable prognostic indicator to evaluate the prognosis of GC.

Roles of platelets in tumor invasion and metastasis: A review.

The invasion and metastasis of malignant tumors are major causes of death. The most common metastases of cancer are lymphatic metastasis and hematogenous metastasis. Hematogenous metastasis often leads to rapid tumor dissemination. The mechanism of hematogenous metastasis of malignant tumors is very complex. Some experts have found that platelets play an important role in promoting tumor hematogenous metastasis. Platelets may be involved in many processes, such as promoting tumor cell survival, helping tumor cells escape immune surveillance, helping tumors attach to endothelial cells and penetrating capillaries for distant metastasis. However, recent studies have shown that platelets can also inhibit tumor metastasis. At present, the function of platelets in tumor progression has been widely studied, and they not only promote tumor cell metastasis, but also have an inhibitory effect. Therefore, in-depth and summary research of the molecular mechanism of platelets in tumor cell metastasis is of great significance for the screening and treatment of cancer patients. The following is a brief review of the role of platelets in the process of malignant tumor metastasis.

Potential productivity loss from uncorrected and under-corrected presbyopia in low- and middle-income countries: A life table modeling study.

Objective: To estimate the burden of potential productivity losses due to uncorrected and under-corrected presbyopia in LMICs among the working-age population in both the cross-sectional and longitudinal manner. Methods: We extracted data for the prevalence of presbyopia from the Global Burden of Diseases (GBD), Injuries, and Risk Factors Study 2019. Data for the gross domestic product (GDP) per capita were extracted from the World Bank database and Central Intelligence Agency's World Factbook. We introduced life table models to construct age cohorts (in 5-year age groups) of the working-age population (aged from 40 to 64 years old) in LMICs, with simulated follow-up until 65 years old in people with and without uncorrected presbyopia. The differences in productivity-adjusted life years (PALYs) lived and productivity between these two cohorts were calculated. The potential productivity loss was estimated based on GDP per capita. The WHO standard 3% annual discount rate was applied to all years of life and PALYs lived. Results: In 2019, there were 238.40 million (95% confidence interval [CI]: 150.92-346.78 million) uncorrected and under-corrected presbyopia cases in LMICs, resulting in 54.13 billion (current US dollars) (95% confidence interval [CI]: 34.34-79.02 billion) potential productivity losses. With simulated follow-up until retirement, those with uncorrected and under-corrected presbyopia were predicted to experience an additional loss of 155 million PALYs (an average loss of 0.7 PALYs per case), which was equivalent to a total loss of US$ 315 billion (an average loss of US$ 1453.72 per person). Conclusions: Our findings highlight the considerable productivity losses due to uncorrected and under-corrected presbyopia in LMICs, especially in a longitudinal manner. There is a great need for the development of enabling eye care policies and programs to create access to eye care services, and more healthcare investment in the correction of presbyopia in the working-age population in LMICs. This study could provide evidences for some potential health-related strategies for socio-economic development.

Assessment of the influence of keratometry on intraocular lens calculation formulas in long axial length eyes.

PURPOSE: Hyperopic surprises tend to occur in axial myopic eyes and other factors including corneal curvature have rarely been analyzed in cataract surgery, especially in eyes with long axial length (≥ 26.0 mm). Thus, the purpose of our study was to evaluate the influence of keratometry on four different formulas (SRK/T, Barrett Universal II, Haigis and Olsen) in intraocular lens (IOL) power calculation for long eyes. METHODS: Retrospective case series. A total of 180 eyes with axial length (AL) ≥ 26.0 mm were divided into 3 keratometry (K) groups: K ≤ 42.0 D (Flat), K ≥ 46.0 D (Steep), 42.0 < K < 46.0 D (Average), and all the eyes were underwent phacoemulsification cataract surgery with Rayner (Hove, UK) 920H IOL implantation. Prediction errors (PE) were compared between different formulas to assess the accuracy of different formulas. Multiple regression analysis was performed to investigate factors associated with the PE. RESULTS: The mean absolute error was higher for all evaluated formulas in Steep group (ranging from 0.66 D to 1.02 D) than the Flat (0.34 D to 0.67 D) and Average groups (0.40 D to 0.74D). The median absolute errors predicted by Olsen formula were significantly lower than that predicted by Haigis formula (0.42 D versus 0.85 D in Steep and 0.29 D versus 0.69 D in Average) in Steep and Average groups (P = 0.012, P < 0.001, respectively). And the Olsen formula demonstrated equal accuracy to the Barrett II formula in Flat and Average groups. The predictability of the SRK/T formula was affected by the AL and K, while the predictability of Olsen and Haigis formulas was affected by the AL only. CONCLUSIONS: Steep cornea has more influence on the accuracy of IOL power calculation than the other corneal shape in long eyes. Overall, both the Olsen and Barrett Universal II formulas are recommended in long eyes with unusual keratometry.

Comparison of Vault Measurements Using a Swept-Source OCT-Based Optical Biometer and Anterior Segment OCT.

Background: To newly describe the vault measurement by using a widely used swept-source OCT-based optical biometer (IOLMaster700) and accessd the accuracy of vault measurement. Methods: This was a retrospective, cross-sectional study. All patients underwent implantable Collamer lens (ICL) implantation surgery without complications. IOLMaster700 and AS-OCT analyses were conducted for each eye on the same day in the same condition. Measurements of anterior chamber depth (ACD), corneal-ICL (C-ICL), and vault values were made and recorded. The repeatability of the IOL Master700 measurements was quantified based upon intraclass correlation coefficient (ICC) values. Correlations between IOL Master700 and AS-OCT measurements made with these different analytical approaches were assessed. The agreement of instruments was evaluated using Bland-Altman plots. Results: The IOLMaster700 instrument yielded highly reliable measurements of vault, C-ICL, and ACD (ICC = 0.996, 0.995, 0.995, respectively). Vault, C-ICL and ACD values as measured using the IOLMaster700, was slightly smaller than that measured via AS-OCT, but these differences were not significant (p = 0.652, p = 0.121 and p = 0.091, respectively). The vault, C-ICL, and ACD measurements by these two instruments were strongly correlated (r = 0.971, r = 0.944, and r = 0.963, respectively; all p < 0.001). The 95% limits of agreement for vault, C-ICL, and ACD measurements between the two devices were-0.08 to 0.08 mm,-0.14 to 0.11 mm, and-0.13 to 0.10 mm, respectively. Conclusions: The IOLMasrer700 can measure implanted ICL vault with a high degree of accuracy and repeatability. Good correlations and agreement were observed between IOLMaster700 and AS-OCT in measuring vault, C-ICL, and ACD measurements.

Predicting Tumor Mutational Burden From Lung Adenocarcinoma Histopathological Images Using Deep Learning.

Tumor mutation burden (TMB) is an important biomarker for tumor immunotherapy. It plays an important role in the clinical treatment process, but the gold standard measurement of TMB is based on whole exome sequencing (WES). WES cannot be done in most hospitals due to its high cost, long turnaround times and operational complexity. To seek out a better method to evaluate TMB, we divided the patients with lung adenocarcinoma (LUAD) in TCGA into two groups according to the TMB value, then analyzed the differences of clinical characteristics and gene expression between the two groups. We further explored the possibility of using histopathological images to predict TMB status, and developed a deep learning model to predict TMB based on histopathological images of LUAD. In the 5-fold cross-validation, the area under the receiver operating characteristic (ROC) curve (AUC) of the model was 0.64. This study showed that it is possible to use deep learning to predict genomic features from histopathological images, though the prediction accuracy was relatively low. The study opens up a new way to explore the relationship between genes and phenotypes.

Comparison of accuracy of intraocular lens power calculation for eyes with an axial length greater than 29.0 mm.

PURPOSE: To evaluate and compare the accuracy of six different formulas (Emmetropia Verifying Optical version 2.0, Kane, SRK/T, Barrett Universal II, Haigis and Olsen) in intraocular lens (IOL) power calculation for extremely long eyes. METHODS: Retrospective case-series. Seventy-three eyes with axial length (AL) ≥ 29.0 mm and underwent phacoemulsification cataract surgery with Rayner (Hove, UK) 920H IOL implantation from January 2018 to March 2020 were included. Prediction errors (PE) were calculated and compared between different formulas to evaluate the accuracy of formulas. Multiple regression analysis was performed to investigate factors associated with the PE. RESULTS: The Kane formula had mean prediction error close to zero (- 0.01 ± 0.51 D, P = 0.841), whereas the EVO 2.0, SRK/T, Barrett Universal II, Haigis and Olsen formulas produced hyperopic outcomes (all P < 0.001). The median absolute error [inter-quartile range] produced by the EVO 2.0, Kane, Barrett Universal II and Olsen formulas showed no significant difference (0.33 D [0.48], 0.30 D [0.44], 0.34 D [0.39], 0.29 D [0.37], respectively, pairwise comparison P > 0.05), but was significantly lower than that of the SRK/T and Haigis formulas (0.85 D [0.66], 0.80 D [0.54], respectively, pairwise comparison P < 0.001). The AL and the PE produced by the SRK/T formula were significantly positively correlated in extremely myopic eyes (ß = 0.248, P < 0.001), whereas the trend was not demonstrated in other formulas. CONCLUSIONS: For cataract patients with axial length greater than 29.0 mm, the accuracy of the EVO 2.0, Kane, Barrett Universal II and Olsen formulas is comparable and significantly better than that of the SRK/T and Haigis formulas.

Prevalence of Visual Impairment in Preschool Children in Southern China.

Purpose: The goal of this study is to assess the prevalence and distribution of visual impairment in preschool children in southern China. Methods: Preschool children aged 36-83 months were enrolled in a vision screening program in Shantou City. Visual acuity test and non-cycloplegic refraction were conducted. According to the American Academy of Ophthalmology (AAO) guidelines, visual impairment was defined as uncorrected visual acuity (UCVA) in either eye <20/50, 20/40, and 20/32 in children aged 36-47, 48-59, and 60-83 months, respectively, as well as an interocular difference (IOD) of ≥ two lines of UCVA. Results: The UCVA test was successfully performed on 7,880 children (94.6% of the enrolled population). A total of 938 (11.9%; 95% CI 11.2-12.6) children were found to have reduced UCVA in the worse eye, and 393 (5%; 95% CI 4.5-5.5) of the children had an IOD of two or more lines. Combining the reduced UCVA with the IOD criteria identified 1,032 (13.1%; 95% CI 12.4-13.8) children with visual impairment. UCVA in preschool children improves with age naturally and boys have slightly better age-adjusted UCVA than girls. Causes of reduced visual acuity included uncorrected refractive error, amblyopia, congenital cataract, and others. The cylindrical diopter in the right eye of children with reduced vison was higher than that of children with normal vision (1.19 ± 1.05 vs. 0.52 ± 0.49, P < 0.001). A total of 146 (1.9%, 95% CI 1.6-2.2) of the preschool children wore spectacles. The proportion of wearing spectacles increased with age (χ2 = 35.714, P < 0.001), but with IOD increasing by.1 logMAR, the odds of wearing spectacles decreased by 44.8%. Conclusion: This study provided data on the prevalence of visual impairment in preschool children in China by large-scale school-based vision screening. Further studies should be conducted to verify the benefit from vision screening.

lncRNA-encoded pep-AP attenuates the pentose phosphate pathway and sensitizes colorectal cancer cells to Oxaliplatin.

Oxaliplatin (L-OHP) is a standard treatment for colorectal cancer (CRC), but chemoresistance is a considerable challenge. L-OHP shows dose-dependent toxicity, and potential approaches that sensitize cancer cells to L-OHP could reduce the dosage. With the development of translatomics, it was found that some lncRNAs encode short peptides. Here, we use ribosome footprint profiling combined with lncRNA-Seq to screen 12 lncRNAs with coding potential, of which lnc-AP encodes the short peptide pep-AP, for their role in L-OHP resistance. Co-IP and LC-MS/MS data show that the TALDO1 protein interacts with pep-AP and that pep-AP suppresses the expression of TALDO1. The pep-AP/TALDO1 pathway attenuates the pentose phosphate pathway (PPP), reducing NADPH/NADP+ and glutathione (GSH) levels and causing ROS accumulation and apoptosis, which sensitizes CRC cells to L-OHP in vitro and in vivo. pep-AP thus might become a potential anticancer peptide for future treatments of L-OHP-resistant CRC.

Gene polymorphism of DNA repair gene X-ray repair cross complementing group 1 and xeroderma pigmentosum group D and environment interaction in non-small-cell lung cancer for Chinese nonsmoking female patients.

An association between genetic polymorphisms in encoding X-ray repair cross complementing group 1 (XRCC1) and encoding xeroderma pigmentosum group D (XPD) and risks of non-small-cell lung cancer (NSCLC) in East Chinese Han population has been observed. Herein we hypothesized that genetic polymorphisms in these two DNA repair genes are likely to be important in the NSCLC in Chinese nonsmoking female patients. We recruited 327 nonsmoking female patients with NSCLC and 342 individuals with benign lung diseases or healthy controls. Genotype frequencies of XRCC1 T-77C, Arg194Trp, Arg280His and Arg399Gln, Pro206Pro, and XPD Asp312Asn and Lys751Gln were calculated after Polymerase Chain Reaction amplification and sequencing. Generalized multifactor dimensionality reduction (GMDR) was used to detect the interactive effect of XRCC1 and XPD gene polymorphisms. The ratio of cooking oil mist exposure history and soot exposure history, and the gene frequencies of XRCC1 T-77C TC + CC, XRCC1 AG + GG, XRCC1 399Gln/Gln, and XPD 751Gln/Gln were higher in female patients with NSCLC than those with benign lung diseases or healthy controls. The haplotypes of XRCC1 T-Arg-Arg-Gln and XRCC1 C-Arg-Arg-Arg were positively associated with the NSCLC occurrence in nonsmoking female patients. GMDR discovered that there was an interactive model of XRCC1 and XPD genes in multiple gene loci. Logistic regression analysis showed that XRCC1 T-77C, XRCC1 Pro206Pro polymorphism, cooking oil mist and soot exposure history and tumor-node-metastasis (TNM) stage were related to NSCLC occurrence for nonsmoking female patients. Taken together, XRCC1 and XPD polymorphisms, cooking oil mist, and soot exposure history may be interactively correlated with NSCLC incidence for nonsmoking female patients.

Single Nucleotide Polymorphisms in the PTPN1 Gene Are Associated with Susceptibility to Esophageal Squamous Cell Carcinoma: A Case-Control Study in Inner Mongolia, China.

OBJECTIVE: This case-control study investigated the association of single nucleotide polymorphisms in the PTPN1 gene with susceptibility to esophageal squamous cell carcinoma (ESCC) in Inner Mongolia, China. METHODS: A total of 302 patients living in Inner Mongolia China who were pathologically diagnosed with ESCC between April 2012 and 2016 were selected for the ESCC group; 373 healthy individuals were selected for the control group. The rs2904268 C>G, rs2230605 A>G, and rs16995309 C>T polymorphisms in the PTPN1 gene were detected by bidirectional polymerase chain reaction amplification of specific alleles. The haplotype frequencies were analyzed by SHEsis software. Binary logistic regression analysis was conducted to analyze risk factors associated with ESCC. RESULTS: Statistical differences between the ESCC and control groups were observed for history of smoking, drinking, and poor eating habits (all p < 0.05). Both the rs2904268 C>G CG and GG genotype frequencies were markedly higher in the ESCC group relative to the control group (both p < 0.05). However, the genotype frequencies of rs2230605 A>G and rs16995309 C>T were similar between the ESCC and control groups (all p > 0.05). Compared with the control group, the ESCC group had notably elevated frequencies of the GGC and GAT haplotypes and significantly reduced frequencies of CGC and GGT haplotypes (all p < 0.05). A history of smoking, drinking, poor eating habits, the rs2904268 C>G CG+GG genotypes, and the GAT haplotype were all identified as risk factors for ESCC (all p < 0.05). CONCLUSION: These results indicated that the PTPN1 gene polymorphism rs2904268 is associated with susceptibility to ESCC in Inner Mongolia.

MicroRNA-218 inhibits the proliferation, migration, and invasion and promotes apoptosis of gastric cancer cells by targeting LASP1.

The present study aims to investigate the effects of microRNA-218 (miR-218) on the proliferation, migration, invasion, and apoptosis of gastric cancer (GC) cells by targeting LIM and SH3 domain protein 1 (LASP1). The GC cells in the logarithmic phase were selected and divided into five groups: the blank group, negative control (NC) group, miR-218 inhibitors group, miR-218 inhibitors + siLASP1 group, and miR-218 mimics + siLASP1 group. The miR-218 expression in each group was also detected by qRT-PCR. The CCK8 assay, Transwell migration, and invasion assays and flow cytometry were performed to determine the effects of miR-218 on cell proliferation, migration, invasion, and apoptosis of GC cells. Western blotting was conducted to measure LASP1 protein expression in GC cells after transfection. The qRT-PCR revealed that the transfection of miR-218 mimics could upregulate the miR-218 expression, and the transfection of miR-218 inhibitors could downregulate the miR-218 expression in the GC cells. Compared with the blank and NC groups, the proliferation, migration, and invasion of GC cells were significantly reduced in the miR-218 mimics, miR-218 inhibitors + siLASP1, and miR-218 mimics + siLASP1 groups but enhanced in the miR-218 inhibitors group. Similarly, compared with the blank and NC groups, the cell apoptosis rates in the miR-218 mimics, miR-218 inhibitors + siLASP1, and the miR-218 mimics + siLASP1 groups were significantly increased, while the miR-218 inhibitors group had a lower apoptosis rate. In conclusion, these results indicate that miR-218 could inhibit the proliferation, migration, and invasion and promote apoptosis of GC cells by downregulating LASP1 expression.

Mutations of RagA GTPase in mTORC1 Pathway Are Associated with Autosomal Dominant Cataracts.

Cataracts are a significant public health problem with no proven methods for prevention. Discovery of novel disease mechanisms to delineate new therapeutic targets is of importance in cataract prevention and therapy. Herein, we report that mutations in the RagA GTPase (RRAGA), a key regulator of the mechanistic rapamycin complex 1 (mTORC1), are associated with autosomal dominant cataracts. We performed whole exome sequencing in a family with autosomal dominant juvenile-onset cataracts, and identified a novel p.Leu60Arg mutation in RRAGA that co-segregated with the disease, after filtering against the dbSNP database, and at least 123,000 control chromosomes from public and in-house exome databases. In a follow-up direct screening of RRAGA in another 22 families and 142 unrelated patients with congenital or juvenile-onset cataracts, RRAGA was found to be mutated in two unrelated patients (p.Leu60Arg and c.-16G>A respectively). Functional studies in human lens epithelial cells revealed that the RRAGA mutations exerted deleterious effects on mTORC1 signaling, including increased relocation of RRAGA to the lysosomes, up-regulated mTORC1 phosphorylation, down-regulated autophagy, altered cell growth or compromised promoter activity. These data indicate that the RRAGA mutations, associated with autosomal dominant cataracts, play a role in the disease by acting through disruption of mTORC1 signaling.