In the present study, we demonstrated that GLTSCR1 decreased the ZO1 transcription elongation rate to provide a longer time window for the splicing factor HuR to recognize the 3′ and 5′ weak splice sites in ZO1 E23, which resulted in E23 inclusion in ZO1 and suppressed CRC progression. This evidence concerns the gene TJP1 and colorectal carcinoma.