Hua-Wen Li

Bio: Hua-Wen Li is an academic researcher from Jinan University. The author has contributed to research in topics: Medicine & Cancer. The author has an hindex of 1, co-authored 2 publications receiving 5 citations. Previous affiliations of Hua-Wen Li include Macau University of Science and Technology.

GALNT14 regulates ferroptosis and apoptosis of ovarian cancer through the EGFR/mTOR pathway.

Abstract: Background: Chemoresistance usually occurs in ovarian cancer. We aimed to explore the mechanisms of chemoresistance. Methods: Western blotting assay was used to detect the expression of GALNT14. Further cell function experiments were performed to investigate the effect of GALNT14 in ovarian cancer. Results: GALNT14 is significantly upregulated in ovarian cancer. Downregulation of GALNT14 significantly inhibits both apoptosis and ferroptosis of ovarian cancer cells. A further mechanism assay illustrated that downregulation of GALNT14 suppresses the activity of the mTOR pathway through modifying O-glycosylation of EGFR. Finally, an additive effect promoting cell death occurs with a combination of an mTOR inhibitor and cisplatin. Conclusion: Our study might provide a promising method to overcome cisplatin resistance for patients with ovarian cancer.

Plasma Alkylresorcinol Metabolite, a Biomarker for Whole-Grain Intake, Is Inversely Associated with Risk of Nonalcoholic Fatty Liver Disease in a Case-Control Study of Chinese Adults.

Abstract: BACKGROUND Epidemiological studies consistently find associations between whole-grain intake and reduced risk of obesity and related metabolic diseases, yet data on the potential of whole grains to prevent fatty liver diseases are scarce. OBJECTIVES To examine whether plasma 3-(3, 5-dihydroxyphenyl)-1-propanoic acid (DHPPA), a biomarker of whole-grain wheat and rye intake, is associated with nonalcoholic fatty liver disease (NAFLD). METHODS This case-control study of Chinese adults enrolled 940 NAFLD cases and 940 age- and sex-matched non-NAFLD controls (mean age: 55.2 years; 65% males). NAFLD diagnosis was defined as individuals whose hepatic ultrasound disclosed hepatic steatosis at any stage, after the exclusion of alcohol abuse and other liver diseases. Fasting plasma DHPPA concentration was measured by high-performance liquid chromatography-tandem mass spectrometry. Multivariate adjusted odds ratios (ORs) and 95% confidence intervals (CI) were estimated to assess the association between plasma DHPPA and NAFLD using conditional logistic regression. RESULTS Plasma concentration of DHPPA was significantly lower in NAFLD patients compared to controls (median: 9.86 nmol/L vs. 10.9 nmol/L, P = 0.002). In multivariable logistic regression models, the ORs (95% CI) for NAFLD across increasing tertiles of plasma DHPPA were 1 (referent), 0.76 (0.54, 1.05) and 0.65 (0.45, 0.93), respectively (P for trend = 0.026). In addition, the inverse associations persisted in subgroups stratified by sex, age, BMI, abdominal adiposity, smoking status, physical activity, diabetes, hypertension, and hyperlipidemia. CONCLUSIONS These results indicate that increased plasma DHPPA concentration is associated with lower risk of NAFLD in Chinese adults, independently of well-known risk factors. Our finding provides evidence to support health benefits of whole-grain consumption on NAFLD. This trial was registered at clinicaltrials.gov as NCT03845868.

Plasma Alkylresorcinol Metabolite, a Biomarker for Whole-Grain Intake, Is Inversely Associated with Risk of Nonalcoholic Fatty Liver Disease in a Case-Control Study of Chinese Adults.

Abstract: BACKGROUND Epidemiologic studies consistently find associations between whole-grain intake and reduced risk of obesity and related metabolic diseases, yet data on the potential of whole grains to prevent fatty liver diseases are scarce. OBJECTIVES To examine whether plasma 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), a biomarker of whole-grain wheat and rye intake, is associated with nonalcoholic fatty liver disease (NAFLD). METHODS This case-control study of Chinese adults enrolled 940 NAFLD cases and 940 age- and sex-matched non-NAFLD controls (mean age: 55.2 y; 65% males). NAFLD diagnosis was defined as individuals whose hepatic ultrasound disclosed hepatic steatosis at any stage, after the exclusion of alcohol abuse and other liver diseases. Fasting plasma DHPPA concentration was measured by LC-MS/MS. Multivariate adjusted ORs and 95% CIs were estimated to assess the association between plasma DHPPA and NAFLD using conditional logistic regression. RESULTS Plasma concentration of DHPPA was significantly lower in patients with NAFLD compared with controls (median: 9.86 nmol/L compared with 10.9 nmol/L, P = 0.002). In multivariable logistic regression models, the ORs (95% CIs) for NAFLD across increasing tertiles of plasma DHPPA were 1 (reference), 0.76 (0.54, 1.05), and 0.65 (0.45, 0.93), respectively (P-trend = 0.026). In addition, the inverse associations persisted in subgroups stratified by sex, age, BMI, abdominal adiposity, smoking status, physical activity, diabetes, hypertension, and hyperlipidemia. CONCLUSIONS These results indicate that increased plasma DHPPA concentration is associated with lower risk of NAFLD in Chinese adults, independently of well-known risk factors. Our finding provides evidence to support health benefits of whole-grain consumption on NAFLD. This trial was registered at clinicaltrials.gov as NCT03845868.

Transcription Factors in Cancer: When Alternative Splicing Determines Opposite Cell Fates.

Abstract: Alternative splicing (AS) is a finely regulated mechanism for transcriptome and proteome diversification in eukaryotic cells. Correct balance between AS isoforms takes part in molecular mechanisms that properly define spatiotemporal and tissue specific transcriptional programs in physiological conditions. However, several diseases are associated to or even caused by AS alterations. In particular, multiple AS changes occur in cancer cells and sustain the oncogenic transcriptional program. Transcription factors (TFs) represent a key class of proteins that control gene expression by direct binding to DNA regulatory elements. AS events can generate cancer-associated TF isoforms with altered activity, leading to sustained proliferative signaling, differentiation block and apoptosis resistance, all well-known hallmarks of cancer. In this review, we focus on how AS can produce TFs isoforms with opposite transcriptional activities or antagonistic functions that severely impact on cancer biology. This summary points the attention to the relevance of the analysis of TFs splice variants in cancer, which can allow patients stratification despite the presence of interindividual genetic heterogeneity. Recurrent TFs variants that give advantage to specific cancer types not only open the opportunity to use AS transcripts as clinical biomarkers but also guide the development of new anti-cancer strategies in personalized medicine.

LncRNA MALAT1/miR-181a-5p affects the proliferation and adhesion of myeloma cells via regulation of Hippo-YAP signaling pathway

Abstract: Multiple myeloma (MM) is a plasma cells malignant proliferative disease, especially in aged people. LncRNAs have been considered as important regulators in MM. This research was to study the effect...

USF1-induced upregulation of LINC01048 promotes cell proliferation and apoptosis in cutaneous squamous cell carcinoma by binding to TAF15 to transcriptionally activate YAP1.

Abstract: Previous studies have revealed that dysregulation of long non-coding RNAs (lncRNAs) can facilitate carcinogenesis. This study aims to investigate the biological role of a certain lncRNA in cutaneous squamous cell carcinoma (CSCC). According to the data of TCGA database, high expression of long intergenic non-protein coding RNA 1048 (LINC01048) is an unfavorable prognostic factor for patients with CSCC. Therefore, we further detected the expression pattern of LINC01048 in CSCC tissues. Obviously, LINC01048 was expressed higher in the CSCC tissues and recurrence tissues compared with that in adjacent normal tissues and non-recurrence tissues. Furthermore, Kaplan–Meier analysis revealed the negative correlation between LINC01048 expression and the overall survival and disease-free survival of CSCC patients. Subsequently, functional assays were conducted to prove the inhibitory effect of silenced LINC01048 on the proliferation and apoptosis of CSCC cells. Mechanistically, LINC01048 was proved to be transcriptionally activated by USF1. Pathway analysis and western blot assay showed that knockdown of LINC01048 led to the activation of Hippo pathway. Moreover, YAP1, a Hippo pathway factor, was positively regulated by LINC01048. Further mechanism investigation revealed that LINC01048 increased the binding of TAF15 to YAP1 promoter to transcriptionally activate YAP1 in CSCC cells. Finally, rescue assays demonstrated that YAP1 involved in LINC01048-mediated CSCC cell proliferation and apoptosis. In conclusion, USF1-induced upregulation of LINC01048 promoted CSCC by interacting with TAF15 to upregulate YAP1.

News about the Role of the Transcription Factor REST in Neurons: From Physiology to Pathology.

Abstract: RE-1 silencing transcription factor (REST) (known also as NRSF) is a well-known transcription repressor whose strong decrease induces the distinction of neurons with respect to the other cells. Such distinction depends on the marked increased/decreased expression of specific genes, accompanied by parallel changes of the corresponding proteins. Many properties of REST had been identified in the past. Here we report those identified during the last 5 years. Among physiological discoveries are hundreds of genes governed directly/indirectly by REST, the mechanisms of its neuron/fibroblast conversions, and the cooperations with numerous distinct factors induced at the epigenetic level and essential for REST specific functions. New effects induced in neurons during brain diseases depend on the localization of REST, in the nucleus, where functions and toxicity occur, and in the cytoplasm. The effects of REST, including cell aggression or protection, are variable in neurodegenerative diseases in view of the distinct mechanisms of their pathology. Moreover, cooperations are among the mechanisms that govern the severity of brain cancers, glioblastomas, and medulloblastomas. Interestingly, the role in cancers is relevant also for therapeutic perspectives affecting the REST cooperations. In conclusion, part of the new REST knowledge in physiology and pathology appears promising for future developments in research and brain diseases.

Ferroptosis and Its Role in Chronic Diseases

Abstract: Ferroptosis, which has been widely associated with many diseases, is an iron-dependent regulated cell death characterized by intracellular lipid peroxide accumulation. It exhibits morphological, biochemical, and genetic characteristics that are unique in comparison to other types of cell death. The course of ferroptosis can be accurately regulated by the metabolism of iron, lipids, amino acids, and various signal pathways. In this review, we summarize the basic characteristics of ferroptosis, its regulation, as well as the relationship between ferroptosis and chronic diseases such as cancer, nervous system diseases, metabolic diseases, and inflammatory bowel diseases. Finally, we describe the regulatory effects of food-borne active ingredients on ferroptosis.