RNA m6A reader YTHDF1 facilitates inflammation via enhancing NLRP3 translation.

N6-methyladenosine (m6A) modification of mRNAs is involved in multiple essential biological processes, dynamically regulated by m6A "writers", "erasers", and "readers". Yet, the detailed functional roles of RNA m6A reader proteins, such as YTHDFs, are largely unknown. Herein we show that YTHDF1 promotes pro-inflammatory IL-1ß production in macrophages during bacterial infections. YTHDF1 overexpression promotes NLRP3 translation. In vivo knockdown of YTHDF1 facilitates survival in a mouse model of sepsis. Thus, YTHDF1 participates in inflammatory responses and subsequent injuries, serving as a new potential therapeutic target in clinical treatment of inflammatory diseases.

LncRNA TUG1 Promotes Growth and Metastasis of Cholangiocarcinoma Cells by Inhibiting miR-29a.

BACKGROUND: As a highly malignant tumor, cholangiocarcinoma poses a serious threat to human life and health, so exploring the mechanisms of its development and progression at a molecular level is of great significance to the diagnosis and treatment of the disease. OBJECTIVE: This study was aimed at investigating the effects and related mechanisms of LncRNA TUG1 on cholangiocarcinoma cells. METHODS: Cholangiocarcinoma tissues and adjacent tissues (n=82 each), human cholangiocarcinoma cell lines (RBE, QBC939, HuH28), and a human normal biliary epithelial cell line (HIBE) were collected. miR-29a-mimics, miR-29a-inhibitor, miR-NC, si-TUG1, pcDNA3.1 TUG1, and NC were transfected into the cholangiocarcinoma cells. qRT-PCR was performed to detect TUG1 and miR-29a expression in the cholangiocarcinoma tissues and cells. Western blotting (WB) was conducted to detect the expression of Bax, Caspase-3, and Bcl-2 in the cells. CCK-8 assay, Transwell, and flow cytometry were carried out to detect cell proliferation, invasion, and apoptosis. Dual luciferase reporter gene assay (DLRGA) was performed to confirm the correlation of TUG1 with miR-29a. RESULTS: TUG1 was highly expressed while miR-29a was poorly expressed in cholangiocarcinoma cells. TUG1 expression was negatively correlated with miR-29a expression, and TUG1 had a relatively high diagnostic value for cholangiocarcinoma. Cell experiments showed that inhibiting TUG1 expression or up-regulating miR-29a expression could inhibit cholangiocarcinoma cells from proliferation and invasion, and promote their apoptosis, while up-regulating TUG1 or inhibiting miR-29a could promote the proliferation and invasion but inhibit the apoptosis. Rescue experiment showed that overexpressing miR-29a could reverse the effects of high TUG1 expression on cholangiocarcinoma cells. DLRGA confirmed that there was a regulatory relationship between TUG1 and miR-29a. CONCLUSION: TUG1 is highly expressed in cholangiocarcinoma tissues. It can promote the growth and metastasis of cholangiocarcinoma cells by inhibiting miR-29a, so it may be a new target for diagnosing and treating cholangiocarcinoma.