1.Research progress on m6A-modified circRNA in oral diseases
Journal of Prevention and Treatment for Stomatological Diseases 2023;31(2):137-141
N6-methyladenosine (m6A) modification is the most abundant RNA modification in eukaryotes and is widely involved in the regulation of RNA nuclear export, splicing, translation and degradation. Increasing evidence shows that m6A methylation modification of circular RNA (circRNA) has great potential in metabolism, immunity and benign and malignant diseases. Here, we review the research status of circRNA m6A methylation modification in physiological processes, malignant tumors and oral diseases. It has been shown that m6A methylation can regulate circRNA by regulating circRNA translation, promoting circRNA nuclear output, and promoting circRNA degradation; M6A-modified circRNA plays a regulatory role in immunity, the reproductive system, myogenesis and development, and malignant tumors; and the M6A methyltransferase METTL3 promotes the occurrence of oral squamous cell carcinoma (OSCC) through m6A modification mediated by YTHDF1. The high expression of METTL14 can effectively reduce the proliferation, migration and invasion of OSCC. There is little research on circRNA m6A methylation modification in the oral cavity, which is limited to preliminary research in ameloblastoma and oral implant bone absorption. It has broad research prospects in the treatment of major oral diseases (such as potential oral malignant diseases and OSCC).
2.Quantitative effect of the expression level of key genes in naringenin synthesis on the accumulation level of target products.
Tingting JIAO ; Jingwen ZHOU ; Sha XU
Chinese Journal of Biotechnology 2019;35(7):1256-1265
Naringenin is a natural flavonoid compound with anti-inflammatory, anti-oxidation, anti-viral, anti-atherosclerosis and other pharmacological activities. It is also an important precursor of other flavonoid synthesis and with great value of application. At present, the production of flavonoids such as naringenin by microbial methods has a low yield due to imbalance of metabolic pathways, which greatly limits its industrial application. In this study, a naringenin-producing strain of Saccharomyces cerevisiae Y-01 was used in the research object. The expression levels of 4-coumaric acid: CoA ligase (4CL), chalcone synthase (CHS) and chalcone isomerase (CHI) were controlled by promoter and copy numbers to investigate the quantitative effect of key enzyme expression level on the accumulation level of target products. The results showed that the correlation between naringenin production and 4CL or CHI expression was not significant while there was a positive correlation with the expression level of CHS. Strain Y-04 with high yield of naringenin was obtained by regulating the expression level of chs gene, and the yield was increased by 4.1-folds compared with the original strain Y-01. This study indicated that CHS is a key regulatory target of naringenin synthesis. Rational regulation of CHS expression can significantly promote the accumulation of naringenin. The related results provide an important theoretical reference for the use of metabolic engineering to strengthen microbial synthesis of important flavonoids such as naringenin.
Flavanones
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metabolism
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Metabolic Engineering
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Saccharomyces cerevisiae
3.Research advances in the degradation of hepatic lipid droplets through the autophagy pathway
Rongzhi WANG ; Linli WANG ; Jingwen JIAO ; Yunfei YU ; Baolong LI
Journal of Clinical Hepatology 2024;40(9):1916-1923
Autophagy is a highly conserved cellular degradation pathway that degrades lipid droplets through a process called “lipophagy”. Lipophagy can selectively recognize lipid substances and degrade them, promoting β oxidation and thereby maintaining the balance of intracellular lipid metabolism. The liver regulates lipid droplet metabolism through lipophagy signaling pathways or key molecules, thereby alleviating hepatic steatosis and improving nonalcoholic fatty liver disease (NAFLD). This article reviews the latest advances in the degradation of hepatic lipid droplets through the three autophagic pathways of macroautophagy, molecular chaperone-mediated autophagy, and microautophagy. The major signaling pathways of AMPK/mTOR-ULK1, ATGL-SIRT1, FGF21-JMJD3, and Akt are involved in the regulation of the lipophagy process and help to maintain the homeostasis of lipid metabolism in the liver, so as to provide new ideas for clinical prevention and treatment of NAFLD.
4.Co-expression of circRNA in oral leukoplakia and oral lichen planus
YANG Jingwen ; SONG Yuhan ; XU siming ; GE Shuyun ; ZHOU Haiwen
Journal of Prevention and Treatment for Stomatological Diseases 2023;31(11):774-781
Objective:
To find any differentially expressed circRNAs in oral leukoplakia (OLK) and oral lichen planus (OLP), to investigate the possible role of circRNAs in the pathogenesis of these two diseases.
Methods:
This study obtained hospital ethical approval. High-throughput sequencing was used to detect differentially expressed circRNAs in OLK, OLP, oral squamous cell carcinoma and normal oral mucosal tissues. CircRNAs were verified by qRT-PCR, enzyme tolerance assays and Sanger sequencing. GO functional analysis and KEGG pathway analysis were performed to predict the functions of circRNAs in OLP. TargetScan and miRanda were applied to predict targeted miRNAs and mRNAs of circRNAs, and ceRNA networks were mapped.
Results:
A total of 49 circRNAs were differentially expressed in OLK and OLP together, including 30 upregulated and 19 downregulated circRNAs. The five circRNAs confirmed with RT-qPCR, including circHLA-C, circRNF13, circTTN, circSEPN2 and circALDH3A2, were all abnormally expressed in OLK and OLP, among which circHLA-C was a key circRNA with trans splice sites, which was validated by expanding the sample size. ROC curve analysis showed that the area under the circHLA-C curve for predicting OLK was 0.955, and the area under the circHLA-C curve for predicting OLP was 0.988. GO functional analysis showed enrichment of many biological processes related to the immune process. The KEGG pathway with the highest enrichment score was "Natural killer cell mediated cytotoxicity". HLA-C was significantly enriched in these processes/pathways. CeRNA network analysis showed that circHLA-C interacted with a variety of miRNAs, such as hsa-miR-26a-5p, hsa-miR-129-5p, and hsa-miR-29a-3p.
Conclusion
Many circRNAs were differentially expressed in both OLK and OLP, circHLA-C being the most elevated. CircHLA-C is valuable for the early diagnosis of OLK and OLP and may serve as a potential biomarker for the diagnosis and prognosis of OLK and OLP.