Purpose: The angiogenesis is among the primary factors that affect tumor recurrence and distant organ metastasis in colorectal cancer (CRC). N6-methyladenosine (m6A) modification is one of the most common chemical modifications in eukaryotic mRNA, especially at the post-transcriptional level. Methyltransferase-like 3 (METTL3) promoting angiogenesis in a variety of tumors has been reported. However, the mechanism of how METTL3 dual-regulates the stability of long non-coding RNAs (lncRNAs) and vascular-related factor RNAs to affect angiogenesis in CRC is unclear. Methods: 64 paired CRC and adjacent normal tissues were collected. In vitro, quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), actinomycin assay, methylated RNA immunoprecipitation (MeRIP) experiment,3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and colony formation assay were performed. The functions were also studied in zebrafish model animals in vivo. Results: We found that the vascular endothelial growth factor A(VEGFA), METTL3 and LINC00662 RNAs were highly expressed in CRC, and that METTL3 was significantly positively correlated with LINC00662 and VEGFA. The protein expression levels of CD31, CD34, VEGFA, m6A and METTL3 were all significantly increased in the CRC tissues. The angiogenesis experiments both in vivo and in vitro found that METTL3 and LINC00662 promoted angiogenesis in CRC. The actinomycin assay indicated that METTL3 maintained the stability of LINC00662 and VEGFA RNAs. In addition, the MeRIP experiment confirmed that the LINC00662 and VEGFA RNAs had METTL3-enriched sites. Conclusion: These findings suggest that METTL3 and LINC00662 may both serve as diagnostic and prognostic predictive biomarkers for CRC and potential targets for anti-vascular therapy.

Background. Colorectal cancer (CRC) is one of the leading causes of cancer deaths worldwide and in China. Early CRC screening is the best approach to reduce its incidence and mortality rates. The ColoDefense test, a multiplex qPCR assay simultaneously detecting both methylated SEPT9 and SDC2 genes, has demonstrated improved clinical performance on either methylation biomarker alone for CRC screening with both blood and stool samples. Method. Leftover blood chemistry test samples from 125 CRC, 35 advanced adenoma, and 35 small polyp patients and 92 healthy control subjects were examined by the ColoDefense test. Among these samples, the levels of three circulating tumor markers, CEA, AFP, and CA19-9, were also measured for 106 CRC, 28 advanced adenoma, and 20 small polyp patients and all control subjects. Results. Due to the smaller volume and extended storage in nonfrozen state, the ColoDefense test with these samples exhibited reduced performance for all stages of CRC and advanced adenomas. The performance of CEA, AFP, and CA19-9 and their various combinations was also evaluated for CRC screening to identify the tumor marker combinations with the best performance. When combined with the ColoDefense test, the identified combinations did improve the clinical performance. Conclusion. These results suggested a rational path towards developing a CRC screening method that takes advantage of leftover blood chemistry test samples. The successful development of such a method will undoubtedly help promote early CRC screening by increasing its accessibility for the general public.

Background: Colorectal adenomas (CRAs) are precancerous lesions of the large intestine presenting as colorectal polyps. At present, the conventional treatment methods for CRA mainly include high-frequency electrocoagulation and electroexcision, biopsy forceps polypectomy, cauterization by laser and microwave, and other endoscopic interventions. The principal advantages conferred by these treatment strategies include less trauma, quick postoperative recovery, and simplicity to perform. However, the higher recurrence rates and insignificant improvement of postoperative symptoms after endoscopic surgery are considerable drawbacks to this approach. Besides, there is currently no effective pharmacotherapy to prevent the recurrence of CRA. Jianpi Lishi Jiedu (JLJ) granules are a form of traditional Chinese medicine (TCM) used to manage postoperative patients with CRA, which has shown a certain degree of efficacy in clinical practice. However, its effectiveness and safety profile have not been convincingly evaluated. The purpose of this study is to evaluate the clinical efficacy and safety profile of JLJ granules in the management of postoperative patients with CRA and to observe the recurrence rate of adenoma in these patients. Methods: A randomized, double-blind, and placebo-controlled clinical trial is performed in this study. A total of 80 postoperative patients with CRA will be randomly classified into the Jianpi Lishi Jiedu granules group or the placebo control group. Patients in both groups shall receive 3 months of intervention, after which medical follow-up and safety evaluation will be performed for all of the patients. The primary outcome is the recurrence rate of adenomas within 12 months. The secondary outcomes are the cardinal TCM symptom scores, minor TCM symptom scores, Bristol Stool Scale, efficacy of TCM symptoms, safety indicators, and blinding assessment. Discussion: In this study, the impact on the recurrence of adenomas and the efficacy and safety of JLJ granules in terms of improving the clinical symptoms of postoperative patients with CRA will be evaluated. Trial registration: Trial registration Chinese Clinical Trial Registry ChiCTR 2100044297. Registered on March 16, 2021