Background: Long non-coding RNAs modulate tumor occurrence through different molecular mechanisms. It had been reported that HNF1A-AS1 (HNF1A Antisense RNA 1) was differently expressed in multiple tumors. The role of HNF1A-AS1 in colorectal cancer was less analyzed, and the mechanism of regulating the cell cycle has not been completely elucidated. Methods: Differentially expressed lncRNAs were screened out from the TCGA database. HNF1A-AS1 was examined in CRC clinical samples and cell lines by RT-qPCR. CCK8 assay, colony formation assay, flow cytometry, transwell assays, tube forming assay and vivo experiments were performed to study the function of HNF1A-AS1 in CRC tumor progression. Bioinformatic analysis, luciferase report assay, RNA pull-down and RIP assays were carried out to explore proteins binding HNF1A-AS1 and the potential downstream targets. Results: Our results showed that HNF1A-AS1 was upregulated in CRC and associated with unfavorable prognosis. HNF1A-AS1 promoted proliferation, migration and angiogenesis, accelerated cell cycle and reduced cell apoptosis in CRC. Bioinformatics prediction and further experiments proved that HNF1A-AS1 could promote CCND1 expression by suppressing PDCD4 or competitively sponging miR-93-5p. Meanwhile, METTL3 mediated HNF1A-AS1 m⁶A modification and affected its RNA stability. HNF1A-AS1/IGF2BP2/CCND1 may act as a complex to regulate the stability of CCND1. Conclusion: In summary, our result reveals the novel mechanism in which m⁶A-mediated HNF1A-AS1/IGF2BP2/CCND1 axis promotes CRC cell cycle progression, along with competitively sponging miR-93-5p to upregulate CCND1, demonstrating its significant role in cell cycle regulation and suggesting that HNF1A-AS1 may act as a potential prognostic marker of colorectal cancer in the future.

Long non-coding RNAs (lncRNAs) are non-coding RNAs that have more than 200 nucleotides and can participate in the regulation of gene expression in various ways. An increasing number of studies have shown that the dysregulated expression of lncRNAs is related to the occurrence and progression of human cancers. LINC00665 is a novel lncRNA, which is abnormally expressed in various human cancers, such as lung cancer, breast cancer, prostate cancer, and glioma. LINC00665 functions in many biological processes of tumor cells, such as cell proliferation, migration, invasion, angiogenesis, and metabolism, and is related to the clinicopathological characteristics of cancer patients. LINC00665 can play biological functions as a ceRNA, directly binding and interacting with proteins, and as an upstream molecule regulating multiple signaling pathways. In this review, we comprehensively summarize the expression level, function, and molecular mechanisms of LINC00665 in different human cancers and emphasize that LINC00665 is a promising new diagnostic, prognostic biomarker, and therapeutic target.