Background Colorectal carcinoma (CRC) is the third most common cancer and second most common cause of cancer-related deaths worldwide. Ribonucleic acid (RNA) N6-methyladnosine (m6A) and methyltransferase-like 3 (METTL3) play key roles in cancer progression. However, the roles of m6A and METTL3 in CRC progression require further clarification. Methods Adenoma and CRC samples were examined to detect m6A and METTL3 levels, and tissue microarrays were performed to evaluate the association of m6A and METTL3 levels with the survival of patients with CRC. The biological functions of METTL3 were investigated through cell counting kit-8, wound healing, and transwell assays. M6A epitranscriptomic microarray, methylated RNA immunoprecipitation-qPCR, RNA stability, luciferase reporter, and RNA immunoprecipitation assays were performed to explore the mechanism of METTL3 in CRC progression. Results M6A and METTL3 levels were substantially elevated in CRC tissues, and patients with CRC with a high m6A or METTL3 levels exhibited shorter overall survival. METTL3 knockdown substantially inhibited the proliferation, migration, and invasion of CRC cells. An m6A epitranscriptomic microarray revealed that the cell polarity regulator Crumbs3 (CRB3) was the downstream target of METTL3. METTL3 knockdown substantially reduced the m6A level of CRB3, and inhibited the degradation of CRB3 mRNA to increase CRB3 expression. Luciferase reporter assays also showed that the transcriptional level of wild-type CRB3 significantly increased after METTL3 knockdown but not its level of variation. Knockdown of YT521-B homology domain–containing family protein 2 (YTHDF2) substantially increased CRB3 expression. RNA immunoprecipitation assays also verified the direct interaction between the YTHDF2 and CRB3 mRNA, and this direct interaction was impaired after METTL3 inhibition. In addition, CRB3 knockdown significantly promoted the proliferation, migration, and invasion of CRC cells. Mechanistically, METTL3 knockdown activated the Hippo pathway and reduced nuclear localization of Yes1-associated transcriptional regulator, and the effects were reversed by CRB3 knockdown. Conclusions M6A and METTL3 levels were substantially elevated in CRC tissues relative to normal tissues. Patients with CRC with high m6A or METTL3 levels exhibited shorter overall survival, and METTL3 promoted CRC progression. Mechanistically, METTL3 regulated the progression of CRC by regulating the m6A–CRB3–Hippo pathway.

Purpose: As there have been few studies on the effects of the receptor for activated C kinase 1 (RACK1) on gastric cancer (GC), we aimed to explore such effects and the mechanism that may be involved. Patients and methods: Normal gastric epithelial cells and six GC cell lines were used to detect the mRNA expression of RACK1. Overexpressing RACK1 was transfected in HGC27 and MGC803 cells. The effects of overexpressing RACK1 on cell viability, migration, and invasion were determined by cell counting kit-8, wound scratch, and Transwell assay, respectively. The expressions of epithelial–mesenchymal transition (EMT) and Wnt/β-catenin signaling related genes were detected using quantitative real-time PCR or Western blot. Wnt pathway agonist LiCl was added into RACK1 overexpressing GC cells, and then cell viability, migration, and invasion were also detected. Results: RACK1 was downregulated in GC cell lines. Under the circumstance that overexpressing RACK1 was successfully transfected in the two lowest RACK1-expressing GC cells, significant inhibition of cell viability, migration, and invasion, promotion to the mRNA and protein expression of E-cadherin, as well as a decrease in the N-cadherin and Snail expressions could be observed. Overexpressing RACK1 also enhanced the protein level of phosphorylation-β-catenin/β-catenin and attenuated c-Jun protein expression. Additionally, LiCl could partially reverse the inhibitory effects of cell viability, migration and invasion by overexpressing RACK. Conclusion: We found RACK1 possibly inhibited epithelial–mesenchymal transition of GC cells through limitation of the Wnt/β-catenin pathway, thereby suppressing cell migration and invasion; RACK1 could also suppress cell growth.

BackgroundThis study evaluated the effects of Modified Yanghe Decoction on pain, disease activity, and functional capacity, and its safety in subjects with ankylosing spondylitis (AS).Material/MethodsA randomized, controlled study of subjects with AS was conducted over 8 weeks to compare the efficacy of the Modified Yanghe Decoction to celecoxib-sulfasalazine therapy. Subjects were evaluated at visit 1, and at weeks 4 and 8 of the trial. The Bath ankylosing spondylitis disease activity index (BASDAI), nocturnal back pain (NBP), total back pain (TBP), patient global disease activity (PGDA), the Bath ankylosing spondylitis functional index (BASFI), and the Bath ankylosing spondylitis metrology index (BASMI) were measured at each time point. Safety was monitored throughout the study through blood, urine, and stool samples, along with heart, liver, and kidney function tests. The ASAS 20 improvement criteria were used as efficacy criteria.ResultsA total of 80 subjects were included. Both treatment groups were effective: 32 subjects (80%) in the Modified Yanghe Decoction group and 34 (85%) in celecoxib-sulfasalazine group met ASAS 20 improvement criteria; no statistically significant difference between groups was observed (P>0.05). Two subjects in the Modified Yanghe Decoction group reported mild diarrhea during the trial. In the celecoxib-sulfasalazine group, 8 subjects experienced upper-abdominal pain; in 3 subjects this was combined with lowered white blood cell count and in 1 subject it was combined with mild proteinuria. This represents a statistically significant difference in safety (P<0.05) between the 2 treatments.ConclusionsThis study demonstrates the efficacy and safety of the Modified Yanghe Decoction in AS treatment, especially for patients who have poor clinical responses, severe adverse reactions, or for patients unable to afford the standard clinical options.

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