Evidence indicates that long non-coding RNAs (lncRNAs) play a critical role in the regulation of tumor cellular processes, such as proliferation, apoptosis, and metastasis. LncRNA CRNDE (Colorectal Neoplasia Differentially Expressed) is located at human chromosome 16 and has been found overexpressed in a variety of cancers including colorectal cancer (CRC). In this paper, we report that lncRNA CRNDE expression was remarkably upregulated in CRC tissues and that lncRNA CRNDE overexpression was positively correlated with advanced pathological stages and larger tumor sizes. In addition, the knockdown of CRNDE significantly suppressed proliferation and caused apoptosis of CRC cells both in vitro and in vivo. Furthermore, RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated that lncRNA CRNDE could epigenetically suppress the expressions of dual-specificity phosphatase 5 (DUSP5) and CDKN1A by binding to EZH2 (the key components of Polycomb repressive complex 2 (PRC2)), thus promoting CRC development. In conclusion, our data suggest that the lncRNA CRNDE promotes the progression of CRC and is a potential therapeutic target for CRC intervention.

Aberrant expression of long noncoding RNAs (lncRNAs) has frequently been reported in cancer studies, including those of colorectal cancer (CRC). Increasing evidence suggests that lncRNAs are significantly correlated with the pathogenesis, development and metastasis of cancer. Loc554202 is a 2166-bp transcript on human chromosome 9p21.3, the expression of which is dysregulated in breast and lung cancer cells. However, its role in CRC remains under investigation. Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to assess the relative expression of Loc554202 in CRC cell lines and tissues. Gain and/or loss of function approaches were used to investigate the potential functional roles in cell proliferation and apoptosis in vitro and in vivo. qRT-PCR, western-blotting and immunohistochemistry were used to evaluate the mRNA and protein expression of apoptosis-related factors. Loc554202 was significantly downregulated in cancerous tissues and CRC cell lines compared with adjacent normal tissue and a normal human intestinal epithelial cell line. Low Loc554202 expression was closely associated with advanced pathologic stage and a larger tumor size. The overexpression of Loc554202 decreased the cell proliferation and induced apoptosis in vitro and hindered tumorigenesis in vivo. Loc554202 regulated cell apoptosis partly through the activation of specific caspase cleavage cascades. Our results suggest that Loc554202 may play an important role in the progression of CRC and could be a candidate prognostic biomarker or a target for new cancer therapies.

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.

The Hippo signaling pathway was found coordinately modulates cell regeneration and organ size. Its dysregulation contributes to uncontrolled cell proliferation and malignant transformation. YAP/TAZ are two critical effectors of the Hippo pathway and have been demonstrated essential for the initiation or growth of most tumors. Noncoding RNAs (ncRNAs), including miRNAs, lncRNAs, and circRNAs, have been shown to play critical roles in the development of many cancers. In the past few decades, a growing number of studies have revealed that ncRNAs can directly or indirectly regulate YAP/TAZ signaling. YAP/TAZ also regulate ncRNAs expression in return. This review summarizes the interactions between YAP/TAZ signaling and noncoding RNAs together with their biological functions on cancer progression. We also try to describe the complex feedback loop existing between these components.