[Corrigendum] METTL3 antagonizes 5­FU chemotherapy and confers drug resistance in colorectal carcinoma.

Subsequently to the publication of the above article, the authors alerted us to the fact that the data shown in Fig. 8I (for the 'Sh­CN / 0' panel) on p. 11 were mistakenly selected from those data belonging to the experiments shown in Fig. 7H (the 'Sh­CN / 0' panel) of this paper during the final assembly of the figures for review. Note that this error did not affect the conclusions reported in this paper, as both Fig. 7H ('Sh­CN / 0') and Fig. 8I ('Sh­CN / 0') show negative controls of the Comet assay, with no obvious trailing. The revised version of Fig. 8, showing the correct data for the 'Sh­CN / 0' panel in Fig. 8I, is shown on the next page. The authors are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish a Corrigendum, and all the authors agree with its publication. Furthermore, the authors apologize to the readership for any inconvenience caused. [International Journal of Oncology 61: 106, 2022; DOI: 10.3892/ijo.2022.5396].

METTL3 antagonizes 5­FU chemotherapy and confers drug resistance in colorectal carcinoma.

Colorectal cancer (CRC) is one of top five leading causes of cancer­associated mortalities worldwide. 5­Fluorouracil (5­FU) is the first­line chemotherapeutic drug in the treatment of CRC; however, its antineoplastic efficiency is limited due to acquired drug resistance. The regulatory mechanism underlying 5­FU chemotherapeutic response and drug resistance in CRC remains largely unknown. The present study identified that silencing of methyltransferase­like 3 (METTL3) suppressed the proliferation and migration of CRC HCT­8 cells. Using cell survival assays, flow cytometric and colony formation analyses, it was revealed that inhibition of METTL3 sensitized HCT­8 cells to 5­FU by enhancing DNA damage and inducing apoptosis in HCT­8 cells under 5­FU treatment. Furthermore, the expression of METTL3 was upregulated in 5­FU­resistant CRC cells (HCT­8R), which contributed to drug resistance through regulation of RAD51 associated Protein 1 (RAD51AP1) expression. Western blotting, immunofluorescence staining and drug sensitivity assays demonstrated that knockdown of METTL3 augmented 5­FU­induced DNA damage and overcame 5­FU­resistance in HCT­8R cells, which could be mimicked by inhibition of RAD51AP1. The present study revealed that the METTL3/RAD51AP1 axis plays an important role in the acquisition of 5­FU resistance in CRC, and targeting METTL3/RAD51AP1 may be a promising adjuvant therapeutic strategy for patients with CRC, particularly for those with 5­FU­resistant CRC.

SLCO3A1, A novel crohn's disease-associated gene, regulates nf-κB activity and associates with intestinal perforation.

BACKGROUND & AIMS: To date, only one gene (TNFSF15) has been identified and validated as a Crohn's disease (CD)-associated gene in non-Caucasian populations. This study was designed to identify novel CD-associated single nucleotide polymorphisms (SNPs)/genes and to validate candidate genes using a functional assay. METHODS: SNPs from 16 CD patients and 16 age- and sex-matched control patients were analyzed using Illumina platform analysis. Subsequently, we expanded the study and followed 53 CD patients and 41 control patients by Sequenom MassArray analysis. Quantitative PCR and immunohistochemical staining were performed to assess mRNA and protein expression of the candidate gene on tissue isolated from CD patients. Genotype was correlated with CD phenotypes. Finally, the candidate gene was cloned and its effect on NF-κB activity assessed using a reporter luciferase assay. RESULTS: SLCO3A1 (rs207959) reached statistical significance in the first-stage analysis (P = 2.3E-02) and was further validated in the second-stage analysis (P = 1.0E-03). Genotype and phenotype analysis showed that the rs207959 (T) allele is a risk allele that alters SLCO3A1 mRNA expression and is associated with intestinal perforation in CD patients. Higher levels of mRNA and protein expression of SLCO3A1 were seen in CD patients compared with the control group. Overexpression of SLCO3A1 induced increased NF-κB activity and increased phosphorylation of P65, ERK, and JNK. Nicotine augmented the activation of NF-κB in the presence of SLCO3A1. CONCLUSIONS: SLCO3A1, a novel CD-associated gene, mediates inflammatory processes in intestinal epithelial cells through NF-κB transcription activation, resulting in a higher incidence of bowel perforation in CD patients.