Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint swelling, joint tenderness and destruction of synovial joints, leading to severe disability. Anti‐inflammatory drugs and disease‐modifying anti‐rheumatic drugs (DMARDs) may improve RA process. However, in most patients the treatment effect is still not satisfactory. Cyclin‐dependent kinase 7 (CDK7) plays a well‐established role in the regulation of the eukaryotic cell division cycle, and recent studies indicated that it exerted anti‐inflammatory effect. In our previous research, we found that inhibition of CDK7 by highly selective inhibitor BS‐181 significantly impeded the development of collagen‐induced arthritis (CIA) mice. However, the underlying mechanism of CDK7 in RA remains to be explored. We elucidated the molecular mechanism of CDK7 inhibition in RA inflammation by administration of CDK7 highly selective inhibitor BS‐181 and siRNA‐CDK7. We found that both IL‐1β, IL‐6, IL‐8 and RANKL transcript levels and IL‐1β/IL‐6 secretion were effectively suppressed by BS‐181 treatment as well as CDK7 knockdown. Furthermore, CDK7 inhibition prevented NF‐κB signalling pathway activation and restrained p65 nuclear translocation. Moreover, CDK7 selective inhibitor BS‐181 also blocked phosphorylation of p65 in MH7A cells. These results strongly indicate that CDK7 inhibition by BS‐181 and siRNA‐CDK7 significantly suppresses rheumatoid arthritis inflammation, which may be via blockage of NF‐κB signalling pathway and IL‐1β/IL‐6 secretion.

Abnormal lipid metabolism is the sign of tumour cells. Previous researches have revealed that the lipolytic pathway may contribute to the progression of colorectal cancer (CRC). However, adipose triglyceride lipase (ATGL) role in CRC cells remains unclear. Here, we find that elevated ATGL positively correlates with CRC clinical stages and negatively associates with overall survival. Overexpression of ATGL significantly promotes CRC cell proliferation, while knockdown of ATGL inhibits the proliferation and promotes the apoptosis of CRC cells in vitro. Moreover, in vivo experiments, ATGL promotes the growth of CRC cells. Mechanistically, ATGL enhances the carcinogenic function of CRC cells via promoting sphingolipid metabolism and CoA biosynthesis pathway‐related gene levels by degrading triglycerides, which provides adequate nutrition for the progression of CRC. Our researches clarify for the first time that ATGL is a novel oncogene in CRC and may provide an important prognostic factor and therapeutic target for CRC.

Effective biomarkers for the diagnosis of colorectal cancer (CRC) are essential for improving prognosis. Imbalance in regulation of N6-methyladenosine (m⁶A) RNA has been associated with a variety of cancers. However, whether the m⁶A RNA levels of peripheral blood can serve as a diagnostic biomarker for CRC is still unclear. In this research, we found that the m⁶A RNA levels of peripheral blood immune cells were apparently elevated in the CRC group compared with those in the normal controls (NCs) group. Furthermore, the m⁶A levels arose as CRC progressed and metastasized, while these levels decreased after treatment. The area under the curve (AUC) of the m⁶A levels was 0.946, which was significantly higher than the AUCs for carcinoembryonic antigen (CEA; 0.817), carbohydrate antigen 125 (CA125; 0.732), and carbohydrate antigen 19-9 (CA19-9; 0.771). Moreover, the combination of CEA, CA125, and CA19-9 with m⁶A levels improved the AUC to 0.977. Bioinformatics and qRT-PCR analysis further confirmed that the expression of m⁶A modifying regulator IGF2BP2 was markedly elevated in peripheral blood of CRC patients. Gene set variation analysis (GSVA) implied that monocyte was the most abundant m⁶A-modified immune cell type in CRC patients’ peripheral blood. Additionally, m⁶A modifications were negatively related to the immune response of monocytes. In conclusion, our results revealed that m⁶A RNA of peripheral blood immune cells was a prospective non-invasive diagnostic biomarker for CRC patients and might provide a valuable therapeutic target.