Methylation-regulated tumor suppressor gene PDE7B promotes HCC invasion and metastasis through the PI3K/AKT signaling pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) has a high mortality rate, and the mechanisms underlying tumor development and progression remain unclear. However, inactivated tumor suppressor genes might play key roles. DNA methylation is a critical regulatory mechanism for inactivating tumor suppressor genes in HCC. Therefore, this study investigated methylation-related tumor suppressors in HCC to identify potential biomarkers and therapeutic targets. METHODS: We assessed genome-wide DNA methylation in HCC using whole genome bisulfite sequencing (WGBS) and RNA sequencing, respectively, and identified the differential expression of methylation-related genes, and finally screened phosphodiesterase 7B (PDE7B) for the study. The correlation between PDE7B expression and clinical features was then assessed. We then analyzed the changes of PDE7B expression in HCC cells before and after DNA methyltransferase inhibitor treatment by MassArray nucleic acid mass spectrometry. Furthermore, HCC cell lines overexpressing PDE7B were constructed to investigate its effect on HCC cell function. Finally, GO and KEGG were applied for the enrichment analysis of PDE7B-related pathways, and their effects on the expression of pathway proteins and EMT-related factors in HCC cells were preliminarily explored. RESULTS: HCC exhibited a genome-wide hypomethylation pattern. We screened 713 hypomethylated and 362 hypermethylated mCG regions in HCC and adjacent normal tissues. GO analysis showed that the main molecular functions of hypermethylation and hypomethylation were "DNA-binding transcriptional activator activity" and "structural component of ribosomes", respectively, whereas KEGG analysis showed that they were enriched in "bile secretion" and "Ras-associated protein-1 (Rap1) signaling pathway", respectively. PDE7B expression was significantly down-regulated in HCC tissues, and this low expression was negatively correlated with recurrence and prognosis of HCC. In addition, DNA methylation regulates PDE7B expression in HCC. On the contrary, overexpression of PDE7B inhibited tumor proliferation and metastasis in vitro. In addition, PDE7B-related genes were mainly enriched in the PI3K/ATK signaling pathway, and PDE7B overexpression inhibited the progression of PI3K/ATK signaling pathway-related proteins and EMT. CONCLUSION: PDE7B expression in HCC may be regulated by promoter methylation. PDE7B can regulate the EMT process in HCC cells through the PI3K/AKT pathway, which in turn affects HCC metastasis and invasion.

Non-linear association and benchmark dose of blood pressure on carotid artery intima-media thickening in a general population of southern China.

Background and aims: This study aimed to evaluate whether there is a J-curve association between blood pressure (BP) and carotid artery intima-media thickening (CAIT) and estimate the effect of the turning point of BP on CAIT. Methods and results: Data from 111,494 regular physical examinations conducted on workers and retirees (aged 18 years or older) between January 2011 and December 2016, exported from the hospital information system, were analyzed. Restricted cubic splines (RCS) logistic regression was employed to access the association of BP with CAIT, and Bayesian benchmark dose methods were used to estimate the benchmark dose as the departure point of BP measurements. All the pnon-linear values of BP measurements were less than 0.05 in the RCS logistic regression models. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) had J-curve associations with the risk of CAIT at a turning point around 120/70 mmHg in the RCS. The benchmark dose for a 1% change in CAIT risk was estimated to be 120.64 mmHg for SBP and 72.46 mmHg for DBP. Conclusion: The J-curve associations between SBP and DBP and the risk of CAIT were observed in the general population in southern China, and the turning point of blood pressure for significantly reducing the risk of CAIT was estimated to be 120.64/72.46 mmHg for SBP/DBP.

Comprehensive analysis of the protein phosphatase 2A regulatory subunit B56ε in pan-cancer and its role and mechanism in hepatocellular carcinoma.

BACKGROUND: B56ε is a regulatory subunit of the serine/threonine protein phosphatase 2A, which is abnormally expressed in tumors and regulates various tumor cell functions. At present, the application of B56ε in pan-cancer lacks a comprehensive analysis, and its role and mechanism in hepatocellular carcinoma (HCC) are still unclear. AIM: To analyze B56ε in pan-cancer, and explore its role and mechanism in HCC. METHODS: The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Profiling Interactive Analysis, and Tumor Immune Estimation Resource databases were used to analyze B56ε expression, prognostic mutations, somatic copy number alterations, and tumor immune characteristics in 33 tumors. The relationships between B56ε expression levels and drug sensitivity, immunotherapy, immune checkpoints, and human leukocyte antigen (HLA)-related genes were further analyzed. Gene Set Enrichment Analysis (GSEA) was performed to reveal the role of B56ε in HCC. The Cell Counting Kit-8, plate cloning, wound healing, and transwell assays were conducted to assess the effects of B56ε interference on the malignant behavior of HCC cells. RESULTS: In most tumors, B56ε expression was upregulated, and high B56ε expression was a risk factor for adrenocortical cancer, HCC, pancreatic adenocarcinoma, and pheochromocytoma and paraganglioma (all P < 0.05). B56ε expression levels were correlated with a variety of immune cells, such as T helper 17 cells, B cells, and macrophages. There was a positive correlation between B56ε expression levels with immune checkpoint genes and HLA-related genes (all P < 0.05). The expression of B56ε was negatively correlated with the sensitivity of most chemotherapy drugs, but a small number showed a positive correlation (all P < 0.05). GSEA analysis showed that B56ε expression was related to the cancer pathway, p53 downstream pathway, and interleukin-mediated signaling in HCC. Knockdown of B56ε expression in HCC cells inhibited the proliferation, migration, and invasion capacity of tumor cells. CONCLUSION: B56ε is associated with the microenvironment, immune evasion, and immune cell infiltration of multiple tumors. B56ε plays an important role in HCC progression, supporting it as a prognostic marker and potential therapeutic target for HCC.

REXO2 up-regulation is positively correlated with poor prognosis and tumor immune infiltration in hepatocellular carcinoma.

BACKGROUND: As a homologous counterpart to the prokaryotic oligonuclease found in the cellular cytoplasm and mitochondrion, REXO2 assumes a pivotal role in the maintenance of mitochondrial homeostasis. Nevertheless, the precise functions and mechanisms by which REXO2 operates within the context of hepatocellular carcinoma (HCC) have hitherto remained unexamined. METHODS: The expression levels of REXO2 in HCC tissues were evaluated through the utilization of the immunohistochemical (IHC) method, and subsequently, the association between REXO2 expression and the clinicopathological characteristics of HCC patients was scrutinized employing the χ2 test. A battery of experimental assays, encompassing CCK8 viability assessment, cell colony formation, wound healing, and transwell assays, were conducted with the aim of elucidating the biological role of REXO2 within HCC cells. Complementary bioinformatics analyses were undertaken to discern potential correlations between REXO2 and immune infiltration in tumor tissues. RESULTS: Our IHC findings have unveiled a notable up-regulation of REXO2 within HCC tissues, and this heightened expression bears the status of an independent prognostic factor, portending an adverse outcome for HCC patients (P < 0.05). Upon the attenuation of REXO2 expression, a discernible reduction in the rates of proliferation, invasion and migration of HCC cells ensued (P < 0.05). Furthermore, transcriptome sequencing analysis has provided insights into the putative influence of REXO2 on the development of HCC through the modulation of TNF and NF-κB signaling pathways. Additionally, our bioinformatics analyses have demonstrated a positive correlation between REXO2 and tumor immune cell infiltration, as well as immune checkpoint CTLA-4. CONCLUSIONS: In summation, our results posit an association between the up-regulation of REXO2 and adverse prognostic outcomes, alongside the involvement of immune-related signaling pathways and tumor immune infiltration within the realm of HCC.

Predicting colorectal cancer risk: a novel approach using anemia and blood test markers.

Background and objectives: Colorectal cancer remains an important public health problem in the context of the COVID-19 (Corona virus disease 2019) pandemic. The decline in detection rates and delayed diagnosis of the disease necessitate the exploration of novel approaches to identify individuals with a heightened risk of developing colorectal cancer. The study aids clinicians in the rational allocation and utilization of healthcare resources, thereby benefiting patients, physicians, and the healthcare system. Methods: The present study retrospectively analyzed the clinical data of colorectal cancer cases diagnosed at the Affiliated Hospital of Guilin Medical University from September 2022 to September 2023, along with a control group. The study employed univariate and multivariate logistic regression as well as LASSO (Least absolute shrinkage and selection operator) regression to screen for predictors of colorectal cancer risk. The optimal predictors were selected based on the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. These predictors were then utilized in constructing a Nomogram Model for predicting colorectal cancer risk. The accuracy of the risk prediction Nomogram Model was assessed through calibration curves, ROC curves, and decision curve analysis (DCA) curves. Results: Clinical data of 719 patients (302 in the case group and 417 in the control group) were included in this study. Based on univariate logistic regression analysis, there is a correlation between Body Mass Index (BMI), red blood cell count (RBC), anemia, Mean Corpuscular Volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet count (PLT), Red Cell Distribution Width-Standard Deviation (RDW-SD), and the incidence of colorectal cancer. Based on the findings of multivariate logistic regression analysis, the variables of BMI and RBC exhibit a decrease, while anemia and PLT demonstrate an increase, all of which are identified as risk factors for the occurrence of colorectal cancer. LASSO regression selected BMI, RBC, anemia, and PLT as prediction factors. LASSO regression and multivariate logistic regression analysis yielded the same results. A nomogram was constructed based on the 4 prediction factors identified by LASSO regression analysis to predict the risk of colorectal cancer. The AUC of the nomogram was 0.751 (95% CI, OR: 0.708-0.793). The calibration curves in the validation and training sets showed good performance, indicating that the constructed nomogram model has good predictive ability. Additionally, the DCA demonstrated that the nomogram model has diagnostic accuracy. Conclusion: The Nomogram Model offers precise prognostications regarding the likelihood of Colorectal Cancer in patients, thereby helping healthcare professionals in their decision-making processes and promoting the rational categorization of patients as well as the allocation of medical resources.

Myc-Associated Zinc Finger Protein Promotes Metastasis of Papillary Thyroid Cancer.

BACKGROUND: Myc-associated zinc finger protein (MAZ) plays a role in cancer progression and metastasis. However, the role and underlying molecular mechanism of MAZ in thyroid cancer have not yet been fully elucidated. This study aimed to explore the clinical significance of MAZ in thyroid cancer tissues, and clarify its mechanism in the occurrence and development of thyroid cancer. METHODS: The expression level of MAZ protein in thyroid cancer tissues was detected by bioinformatics analysis and immunohistochemistry (IHC). The relationship between the expression level of MAZ and clinicopathological characteristics of thyroid cancer patients was analyzed by multivariate logistic regression analysis. Quantitative reverse-transcription polymerase chain reaction (RT-qPCR) was used to detect the mRNA expression level of MAZ in thyroid cancer cell lines. After MAZ knockdown cell lines were constructed, wound healing and Transwell assays were used to detect the migratory and invasive abilities of cancer cells. RESULTS: The results of IHC showed that the expression level of MAZ protein in thyroid cancer tissues was higher than that in normal adjacent thyroid tissues (p < 0.05), which was consistent with the high expression level of MAZ in thyroid cancer tissues found in The Cancer Genome Atlas (TCGA) database. The results of multivariate logistic regression analysis indicated that the expression level of MAZ was correlated with tumor diameter and tumor capsule of thyroid cancer patients. Moreover, patients with the high MAZ expression level had shorter overall and disease-free survival compared with thyroid cancer patients with the low MAZ expression level (p < 0.05). Further cell function assays indicated that downregulation of MAZ expression level could inhibit the migration and invasion of thyroid cancer cell lines. Moreover, the expression level of epithelial-mesenchymal transition (EMT)-related factor fibronectin 1 (FN1) was obtained from the RNA-seq of MAZ knockdown in thyroid cancer cells. RT-qPCR confirmed that the expression level of FN1 was elevated in MAZ knockdown cell lines (p < 0.05). Bioinformatics analysis indicated that the expression level of FN1 was upregulated in thyroid cancer tissues and had a negative relationship with the expression level of MAZ, as evidenced by correlation analysis. CONCLUSIONS: A high expression level of MAZ in thyroid cancer tissues was associated with a poor prognosis of patients. MAZ could affect the progression of thyroid cancer by inducing the EMT process.

Prognostic Significance of ZP3 in Hepatocellular Carcinoma.

OBJECTIVE: The study aims to explore the prognostic significance of zona pellucida glycoprotein 3 (ZP3) in hepatocellular carcinoma (HCC) tissues. METHODS: The expression of ZP3 protein in HCC tissues was detected by immunohistochemistry (IHC) to study its effects on the clinicopathological characteristics and prognosis of HCC patients. The Cancer Genome Atlas (TCGA) database was used to confirm the expression of ZP3 in HCC tissues, and Gene set enrichment analysis (GSEA) was performed to obtain potential ZP3-related pathways in HCC. RESULTS: IHC detection found that ZP3 had a high expression in HCC tissues and was associated with cirrhosis and hepatitis B virus infection in HCC patients (p<0.05). TCGA database also showed that ZP3 was up-regulated in HCC tissues. Further survival evaluation confirmed that ZP3 expression caused an impact on the overall survival time and disease-free survival time of HCC patients (p<0.05), implying a potential role in HCC prognosis. GSEA analysis indicated that the 187 differential gene sets were mainly involved in 10 signaling pathways, including 5 up-regulated and 5 down-regulated pathways. CONCLUSION: High expression of ZP3 in HCC tissues is found to have an important role in HCC development and prognosis.

Clinical Significance of TUBGCP4 Expression in Hepatocellular Carcinoma.

We aim to investigate the expression and clinical significance of the tubulin gamma complex-associated protein 4 (TUBGCP4) in hepatocellular carcinoma (HCC). The mRNA expression of TUBGCP4 in HCC tissues was analyzed using The Cancer Genome Atlas (TCGA) database. Paired HCC and adjacent nontumor tissues were obtained from HCC patients to measure the protein expression of TUBGCP4 by immunohistochemistry (IHC) and to analyze the relationship between TUBGCP4 protein expression and the clinicopathological characteristics and the prognosis of HCC patients. We found that TUBGCP4 mRNA expression was upregulated in HCC tissues from TCGA database. IHC analysis showed that TUBGCP4 was positively expressed in 61.25% (49/80) of HCC tissues and 77.5% (62/80) of adjacent nontumor tissues. The Chi-square analysis indicated that the positive rate of TUBGCP4 expression between HCC tissues and the adjacent nontumor tissues was statistically different (P < 0.05). Furthermore, we found that TUBGCP4 protein expression was correlated with carbohydrate antigen (CA-199) levels of HCC patients (P < 0.05). Further, survival analysis showed that the overall survival time and tumor-free survival time in the TUBGCP4 positive group were significantly higher than those of the negative group (P < 0.05), indicating that the positive expression of TUBGCP4 was related to a better prognosis of HCC patients. COX model showed that TUBGCP4 was an independent prognostic factor for HCC patients. Our study indicates that TUBGCP4 protein expression is downregulated in HCC tissues and has a relationship with the prognosis of HCC patients.

Prognostic significance and immune characteristics of CMTM4 in hepatocellular carcinoma.

BACKGROUND: Previous study has shown that chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family member 4 (CMTM4) can bind and maintain programmed cell death ligand 1 (PD-L1) expression to promote tumor progression by alleviating the suppression of tumor-specific T cell activity, suggesting its potential role in tumor immunotherapy. However, the role of CMTM4 in tumor immunity has not been well clarified, especially in hepatocellular carcinoma (HCC). METHODS: The protein expression of CMTM4/PD-L1/CD4/CD8 was detected by immunohistochemistry (IHC) detection in 90 cases of HCC tissues. The mRNA expression profiles and related prognosis data were obtained from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC). Two immune therapy cohorts were from Imvigor210 and GSE176307. RESULTS: Though the single protein expression of CMTM4, PD-L1, CD4 or CD8 in HCC tissues by IHC detection didn't show a significant relationship with the prognosis of HCC patients, we found that high co-expression of CMTM4/PD-L1/CD4 showed a good prognosis of HCC patients. Further Timer 2.0 analysis identified that HCC patients with high expression of CMTM4/PD-L1 and high infiltration of CD4+ T cells had a better overall survival than those with low infiltration of CD4+ T cells. Moreover, a series of bioinformatics analyses revealed that CMTM4-related genes posed important effects on prognosis and immunity in HCC patients, and CMTM4 had a positive correlation with infiltration of CD4+ and CD8+ T cells in HCC. At last, we used two immunotherapy cohorts to verify that the combination of CMTM4 with PD-L1 could improve the prognosis of tumor patients underwent immunotherapy. CONCLUSIONS: CMTM4 and PD-L1 co-expression with T cell infiltration shows prognostic significance in HCC, suggesting combined effect from multiple proteins should be considered in HCC treatment.

hsa-miR-9-5p-Mediated TSPAN9 Downregulation Is Positively Related to Both Poor Hepatocellular Carcinoma Prognosis and the Tumor Immune Infiltration.

Tetraspanins (TSPANs) play crucial roles in cell adhesion, migration, and metastasis of human cancer. However, there is no study in revealing the aspects of TSPAN9 traits and its functions in hepatocellular carcinoma (HCC) prognosis. Our study is the first to portray the TSPAN9 expression in HCC tissues with immunohistochemistry (IHC) analysis. Subsequently, a series of bioinformatics analyses such as expression estimation, survival assessment, and correlation analysis were implemented to dig out the possible upstream noncoding RNAs (ncRNAs) for TSPAN9 in HCC. In this way, the relevance within TSPAN9 and tumor immunity was then explored. We found that the TSPAN9 was downregulated in HCC tissues and had a correlation with HCC prognosis. Furthermore, we identified that the AL139383.1-hsa-miR-9-5p axis was the upstream ncRNA-related pathway most associated with TSPAN9 in HCC. Besides that, expression of TSPAN9 held a significantly negative correlation with tumor immunocyte infiltration as well as immune checkpoint CTLA4. TSPAN9-related immunomodulators were mainly enriched in T cell activation, leukocyte cell-cell adhesion, regulation of T cell activation, and regulation of leukocyte cell-cell adhesion signaling pathway. In conclusion, our results indicated that hsa-miR-9-5p-mediated downregulation of TSPAN9 was associated with poor HCC prognosis, immune-related signaling pathway, and tumor immune infiltration.

Hb New York, preliminary results concerning the hematologic characteristics and the effects on thalassemia.

BACKGROUND: The hematological phenotype and genotype analysis of hemoglobin New York (Hb New York) combined with α or ß thalassemia has been rarely reported, and whether there is any effect of Hb New York on thalassemia has not been well explored. METHODS AND RESULTS: In this study, peripheral blood samples from 346 Hb New York carriers were collected for blood cell parameter analysis. When comparing Hb New York heterozygotes, Hb New York combined with α0 thalassemia or α+ thalassemia, we found that the differences in hemoglobin (HGB), MCV and MCH values were statistically significant (P < 0.05). The HGB, MCV and MCH values of α thalassemia patients were not different from Hb New York combined with α thalassemia group (P > 0.05). When Hb New York heterozygotes were compared to Hb New York combined with ß0 thalassemia or ß+ thalassemia, the differences in MCV and MCH values were statistically significant (P < 0.05). However, the differences in MCV and MCH values were not statistically significant between Hb New York combined with ß thalassemia and ß thalassemia (P > 0.05). CONCLUSIONS: Our study shows that the hematological characteristics of Hb New York combined with thalassemia are similar to the corresponding thalassemia, and Hb New York does not aggravate the clinical manifestations of thalassemia.

Roles of Myc-associated zinc finger protein in malignant tumors.

As an important transcription factor that is widely expressed in most tissues of the human body, Myc-associated zinc finger protein (MAZ) has been reported highly expressed in many malignant tumors and thought to be a promising therapeutic target for cancer treatment. In this review, we aim to offer a comprehensive understanding of MAZ regulation in malignant tumors. The carboxy terminal of MAZ protein contains six C2H2 zinc fingers, and its regulation of transcription is based on the interaction between the GC-rich DNA binding sites of target genes and its carboxy-terminal zinc finger motifs. MAZ protein has been found to activate or inhibit the transcriptional initiation process of many target genes, as well as play an important role in the transcriptional termination process of some target genes, so MAZ poses dual regulatory functions in the initiation and termination process of gene transcription. Through the transcriptional regulation of c-myc and Ras gene family, MAZ poses an important role in the occurrence and development of breast cancer, pancreatic cancer, prostate cancer, glioblastoma, neuroblastoma, and other malignant tumors. Our review shows a vital role of MAZ in many malignant tumors and provides novel insight for cancer diagnosis and treatment.

Downregulated CMTM8 Correlates with Poor Prognosis in Gastric Cancer Patients.

This study aimed to examine the expression and clinical significance of chemokine-like factor-like MARVEL transmembrane domain-containing family member 8 (CMTM8) in gastric cancer (GC). The mRNA and protein expression of CMTM8 were detected by bioinformatics analysis and immunohistochemistry (IHC), respectively. Bioinformatics analysis found that there was a high mRNA expression of CMTM8 in GC tissues, but failed to identify a significant relationship with the clinicopathological features or prognosis of GC patients. However, IHC results showed that the positive expression of CMTM8 protein in GC tissues was significantly lower than that of adjacent nontumor tissues and correlated with differentiation, tumor node metastasis stage, and distal metastasis of GC patients (p < 0.05). Moreover, the survival time of GC patients with negative CMTM8 protein expression group was shorter than that of positive CMTM8 protein expression group by Kaplan-Meier survival analysis (p < 0.05). Cox proportional hazards model (COX) regression analysis indicated that CMTM8 protein was an independent protective factor for the overall survival of GC patients. Further Gene Set Enrichment Analysis suggested that CMTM8 may be involved in regulating the calcium signaling pathway, cell adhesion molecules, and cytokine-cytokine receptor interaction in GC. Our study shows that CMTM8 protein is downregulated in GC tissues, and CMTM8 protein expression is related to GC metastasis and the prognosis of GC patients.

Expression and clinical significance of CMTM1 in hepatocellular carcinoma.

BACKGROUND: CKLF Like Marvel Transmembrane Domain Containing 1 (CMTM1) plays a role in breast cancer and lung cancer, but studies on the occurrence and development of CMTM1 in hepatocellular carcinoma (HCC) have not been reported. METHODS: The Cancer Genome Atlas (TCGA) database and immunohistochemistry (IHC) were used to detect CMTM1 expression in HCC tissues. The relationship between CMTM1 expression and the clinicopathological characteristics of HCC patients was analyzed by chi-square test, and the relationship between CMTM1 expression and the prognosis of HCC patients was tested by the Kaplan-Meier model. RESULTS: Bioinformatics analysis showed that the mRNA expression of CMTM1 was upregulated in HCC tissues, and low expression of CMTM1 is associated with longer disease-free survival in patients with HCC. Similarly, the survival time of HCC patients in CMTM1 high expression group was significantly shorter than that in CMTM1 low expression group. IHC detection indicated that CMTM1 protein was highly expressed in both HCC and adjacent non-tumor tissues, with a positive expression in 84% (63/75) of HCC tissues and 89.3% (67/75) of adjacent non-tumor tissues. Moreover, CMTM1 expression was related to family history and TNM stage of HCC patients (P < 0.05), but had no relationship with other clinicopathological characteristics. The survival analysis based on IHC results showed that the prognosis of HCC patients in CMTM1 negative group was significantly poorer than that in CMTM1 positive group (P < 0.05). CONCLUSION: CMTM1 has a high expression in HCC tissues and is related to the prognosis of HCC patients.

Clinical Significance of POM121 Expression in Lung Cancer.

Aims: The aim of this study was to examine the RNA and protein expression levels and clinical significance of the pore membrane protein 121 kDa (POM121) in lung cancer. Materials and Methods: Paired lung cancer and adjacent nontumor tissues were obtained from lung cancer patients to measure the expression of POM121 by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. Patient clinical and pathological data were collected to analyze their relationships with POM121 protein expression levels by chi-square test and log-rank test, respectively. Results: POM121 mRNA and protein expression were both upregulated in lung cancer tissues. POM121 protein expression was observed in 48.00% (36/75) of lung cancer tissues and 25.33% (19/75) of adjacent nontumor tissues. A chi-square analysis indicated that this difference was statistically significant (p < 0.05). Furthermore, we found that POM121 protein expression was correlated with gender, tumor node metastasis stage, and lymphatic metastasis (p < 0.05). In addition, we found a significant relationship among POM121 expression, gender, and metastasis based on a multivariate logistic regression analysis. A Kaplan-Meier survival analysis indicated that lung cancer patients with POM121 expression had a poorer prognosis than those without POM121 expression (p < 0.05). Conclusion: POM121 protein expression is associated with lung cancer metastasis and is a potential prognostic biomarker for lung cancer patients.

M6A Demethylase FTO Plays a Tumor Suppressor Role in Thyroid Cancer.

The purpose of this study was to investigate the expression and clinical significance of N6-methyladenosine demethylase FTO in thyroid cancer. Bioinformatic analysis showed that FTO expression was downregulated in thyroid cancer tissues and correlated with lymph node metastasis in thyroid cancer patients. We conducted experimental verification by collecting Asian samples. The results of quantitative reverse transcription-PCR showed that the mRNA expression of FTO in the blood of 30 thyroid cancer patients was lower than that of the control population. At the same time, we found that FTO expression was negative in tissues of 16/56 (28.57%) thyroid cancer cases and 4/40 (10.00%) nontumor thyroid cases through the immunohistochemical method, indicating a lower FTO expression in thyroid cancer tissues than nontumor thyroid tissues (p < 0.05). In addition, the protein expression of FTO was significantly related to the tumor grade and lymph node metastasis in thyroid cancer patients (p < 0.05), but not to other clinicopathological features. Multivariate logistic regression analysis showed that FTO expression was an independent risk factor for tumor grade. Survival analysis showed no significant difference in the disease-free survival time of thyroid cancer patients between high expression and low expression groups of FTO. Furthermore, bioinformatic analysis found that promoter DNA methylation and copy number variation might cause downregulated FTO and then affect TP53 pathways in thyroid cancer. We found that FTO expression was downregulated in thyroid cancer tissues and related to the progression of thyroid cancer, suggesting a tumor suppressor role of FTO in thyroid cancer.

Retraction Note to: Correlations between chromobox homolog 8 and key factors of epithelial-mesenchymal transition in hepatocellular carcinoma.

[This retracts the article DOI: 10.1186/s12935-019-1063-z.].

Potential role of CFTR in bisphenol A-induced malignant transformation of prostate cells via mitochondrial apoptosis.

Bisphenol A (BPA) is an environmental endocrine disruptor and a risk factor for prostate cancer. The cystic fibrosis transmembrane conductance regulator (CFTR) is proposed to be a prostate cancer suppressor in some recent researches. However, the potential role and mechanism of CFTR in BPA-induced prostate cancer cells has not been well identified. In this study, BPA decreased the viability of human normal prostate RWPE-1 cells detected with a CCK-8 kit. The capacity of the cell line on soft agar colony formation, wound healing, and transwell invasion indicated malignant transformation induced by BPA. Western blot analysis demonstrated that the levels of CFTR and Bcl-2 decreased, whereas Bax level increased, and ELISA detection showed a decreased ATP level in BPA-exposed cells. Cell apoptosis was analyzed with Annexin V-FITC Detection Kit by flow cytometry. However, no significant difference was observed in cell viability and apoptosis rates compared to normal RWPE-1 cells. Our research revealed a potential role of CFTR in BPA-induced malignant transformation via mitochondrial apoptosis of normal prostate cells.

Manganese induced nervous injury by α-synuclein accumulation via ATP-sensitive K(+) channels and GABA receptors.

Manganese (Mn) is an environmental pollutant having a toxic effect on Parkinson's disease, with significant damage seen in the neurons of basal ganglia. Hence, Mn pollution is a public health concern. A Sprague-Dawley rat model was used to determine the damage to basal nuclei, and the effect of Mn intake was detected using the Morris water maze test and transmission electron microscopy. The SH-SY5Y cell line was exposed to Mn, and downstream signaling was assessed to determine the mechanism of toxicity. Mn exposure injured neurons, repressing GABAAR receptors and inducing GABABR receptors. The synergistic effect of the GABABR receptor and Kir6.1-SUR1 or Kir6.2-SUR1 was found to be one of the potential factors for the secretion of α-synuclein. The accumulation of α-synuclein regulated downstream factors calmodulin (CAM) cAMP response element-binding protein (CREB), thereby impairing learning and memory. Other genes downstream of CREB, rather than the feedback regulation of CREB, and brain-derived neurotrophic factor might also be involved.

Down-Regulated CMTM2 Promotes Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma.

BACKGROUND: Our recent study identified that human chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family member 2 (CMTM2) was deregulated in hepatocellular carcinoma (HCC) tissues and posed as a potential tumor suppressor. However, the mechanism of CMTM2 in HCC occurrence and development has not been well elaborated. MATERIALS AND METHODS: The expression of CMTM2 was knocked-down by RNA interruption in Huh-7 and SMMC7721 cells. Cell proliferation ability was detected by CCK8 test and colony formation assay. The cell invasion and migration were measured by wound healing and Transwell assay. RESULTS: We found that the cell proliferation was significantly increased by interruption of CMTM2 expression, both in Huh-7 and SMMC7721 cells. Moreover, down-regulated CMTM2 could promote the invasion and migration ability of HCC cells through inducing the epithelial-mesenchymal transition (EMT) process. We further discovered that both the expression of CMTM2 and the EMT-associated marker E-cadherin were decreased in the same thirty cases of HCC tissues compared with the corresponding adjacent non-tumor tissues. Pearson correlation test showed that there was a significantly positive correlation between CMTM2 and E-cadherin in HCC tissues (P<0.05). CONCLUSION: Based on the results of cell model and HCC tissues, our study suggests that down-regulated CMTM2 promotes HCC metastasis through inducing the EMT process.