No abstract

Licoricidin, a type of isoflavonoid, is extracted from the root of Glycyrrhiza glabra. It has been widely proven that licoricidin possesses multiple biological activities, including anti-cancer effects and a powerful antimicrobial effect against Helicobacter pylori (H. pylori). However, the exact mechanism of licoricidin against gastric cancer remains unclear. In this study, we comprehensively explored the effects of licoricidin on MGC-803 gastric cancer cells in vitro and in vivo and further elucidated its mechanism of action. Our results revealed that licoricidin exhibited multiple anti-gastric cancer activities, including suppressing proliferation, inducing apoptosis, arresting the cell cycle in G0/G1 phase, and inhibiting the migration and invasion abilities of MGC-803 gastric cancer cells. In addition to this, a total of 5861 proteins were identified by quantitative proteomics research strategy of TMT labeling, of which 19 differential proteins (two upregulated and 17 downregulated) were screened out. Combining bioinformatics analyses and the reported roles in cancer progression of the 19 proteins, we speculated that isoprenyl carboxyl methyltransferase (ICMT) was the most likely target of licoricidin. Western blot assays and IHC assays subsequently proved that licoricidin significantly downregulated the expression of ICMT, both in MGC-803 cells and in xenograft tumors. Moreover, licoricidin effectively reduced the level of active Ras-GTP and blocked the phosphorylation of Raf and Erk, which may be involved in its anti-gastric cancer effects. In summary, we first demonstrated that licoricidin exerted favorable anti-gastric cancer activities via the ICMT/Ras pathway, which suggests that licoricidin, as a natural product, could be a novel candidate for the management of gastric cancer.

Tumour cells change their metabolic patterns to support high proliferation rates and cope with oxidative stress. The lncRNA ELFN1-AS1 is highly expressed in a wide range of cancers and is essential to the proliferation and apoptosis of tumour cells. Nevertheless, its function in the metabolic reprogramming of tumour cells is unclear. Here we show that ELFN1-AS1 promotes glucose consumption as well as lactate and NADPH production. Database searching, bioinformatics analysis, RNA immunoprecipitation (RIP) and RNA pull-down assays show that ELFN1-AS1 enhances glucose-6-phosphate dehydrogenase ( G6PD ) expression and activates the pentose phosphate pathway (PPP) by promoting TP53 degradation. In addition, luciferase reporter assay and chromatin immunoprecipitation (ChIP) show that YY1 binds to the ELFN1-AS1 promoter to promote transcriptional activation of ELFN1-AS1 . Consistent with the in vitro experiments, knockdown of ELFN1-AS1 impedes the growth of tumours transplanted into mice by inhibiting the expression of G6PD . In conclusion, this study reveals that ELFN1-AS1 activates the PPP, and validates the regulatory role of the YY1 / ELFN1-AS1 / TP53 / G6PD axis in colorectal cancer.

Background and Aim Long non‐coding RNA (lncRNA) TNK2 AS1 is a noncoding RNA with the capability of affecting microRNAs (miRNAs) levels and gene expression. The study was designed to investigate the mechanism of TNK2 AS1 in gastric cancer. Methods The loss and gain of function of TNK2 AS1 were investigated by analyzing the malignant behavior of AGS cells including the abilities of migration, invasion, and epithelial‐mesenchymal transition (EMT) process via wound healing and transwell assay, as well as western blot. The targeting relationship of LncRNA TNK2 AS1 was analyzed through searching bioinformatics database, luciferase reporter assay, and RNA immunoprecipitation (RIP) assay. Tumor‐bearing experiment in nude mice was performed to further confirm the regulatory role of TNK2 AS1 in vivo. Immunofluorescence assay for Ki67 expression was carried out in tumor tissues of mice model. Results The results showed that TNK2 AS1 overexpression promoted the malignant behaviors of AGS cells, which could be weakened by miR‐125a‐5p mimic addition. In addition, Jumonji, At‐rich interaction domain (JARID2), and phosphatidylinositol 3 kinase (PI3K)/AKT pathway were regulated by TNK2‐AS1/miR‐125a‐5p axis. In vivo, TNK2 AS1/miR‐125a‐5p axis promoted tumor growth and led to increases in green fluorescence intensity and vimentin expression and a decrease in E‐cadherin level, which could be mediated by JARID2 and PI3K/AKT pathway. Conclusion Therefore, a conclusion was drawn that TNK2‐AS1/miR‐125a‐5p promoted the progression of gastric cancer.