Long noncoding RNA RP11-757G1.5 sponges miR-139-5p and upregulates YAP1 thereby promoting the proliferation and liver, spleen metastasis of colorectal cancer

Abstract

Background: Accumulating evidence indicates that long non-coding RNAs (lncRNAs) acting as crucial regulators in tumorigenesis. However, its biological functions of lncRNAs in colorectal cancer (CRC) have not been systematically clarified. Methods: An unbiased screening was performed to identify disregulated lncRNAs revealed to be implicated in CRC carcinogenesis according to an online-available data dataset. In situ hybridization (ISH), RT-qPCR and RNA fluorescence in situ hybridization (RNA-FISH) were applied to detect RP11-757G1.5 expression in CRC tissues and cell lines. The associations of RP11-757G1.5 with clinicopathological characteristics were analyzed. Their effects on prognosis were analyzed by the Kaplan-Meier analysis, Log-rank test, Univariate and Multivariate Cox regression analysis. The potential biological function of RP11-757G1.5 in CRC was investigated by Colony formation, Edu cell proliferation, Flow cytometry, Wound healing and Transwell assays. Bioinformatics binding site analysis, Luciferase reporter assay, Ago2 immunoprecipitation assays, RNA pull-down assay, RT-qPCR and Western blotting were utilized to demonstrate the mechanism of RP11-757G1.5 acts as a molecular sponge of miR-139-5p to regulate the expression of YAP1. Finally, we further explore the potential role of RP11-757G1.5 in CRC orthotopic xenografts in vivio . Results: We discovered a novel oncogenic lncRNA RP11-757G1.5, that was overexpressed in CRC tissues, especially in aggressive cases. Moreover, up-regulation of RP11-757G1.5 strongly correlated with poor clinical outcomes of patients with CRC. Functional analyses revealed that RP11-757G1.5 promoted cell proliferation in vitro and in vivo . Furthermore, RP11-757G1.5 stimulated cell migration and invasion in vitro and in vivo . Mechanistic studies illustrated that RP11-757G1.5 regulated the expression of YAP1 through sponging miR-139-5p and inhibiting its activity thereby promoting CRC progression and development. Conclusions: Altogether, these results reveal a novel RP11-757G1.5/miR-139-5p/YAP1 regulatory axis that participates in CRC carcinogenesis and progression.

LncRNA KCNQ1OT1 Secreted by Tumor Cell-Derived Exosomes Mediates Immune Escape in Colorectal Cancer by Regulating PD-L1 Ubiquitination via MiR-30a-5p/USP22

“…In addition, lncRNAs also act as competing endogenous RNA (ceRNA), interacting with miRNAs, and by affecting the expression of messenger RNA (mRNA) ( Li S. et al, 2020 ). Zhu et al (2020) found a new type of oncogenic lncRNA RP11-757G1.5 through microarray analysis, which is overexpressed in CRC tissues, especially in aggressive cases. In addition, the upregulation of RP11-757G1.5 is closely related to the adverse clinical outcome of CRC patients.…”

“…Further functional analysis showed that RP11-757G1.5 can promote cell proliferation in vitro and in vivo . The mechanism for this phenomenon is that RP11-757G1.5 regulates the expression of YAP1 and promotes the development of CRC by competitively binding miR-139-5p to inhibit its activity ( Zhu et al, 2020 ). In this study, we combined the previous research results to screen and verify the high expression of lncRNA KCNQ1OT1.…”

Revealing potential immunotherapy targets through analysis of a ceRNA network in human colon adenocarcinoma

“…Salmena et al proposed the competitive endogenous RNA (ceRNA) hypothesis, which suggests that mRNAs, lncRNAs, and other non-coding RNAs can be used as natural miRNA "sponges" that participate in the process of RNA degradation and post-translational modification together with ordinary miRNA response elements (MREs) (8). Previous studies have confirmed that non-coding RNAs are involved in tumorigenesis, invasion, metastasis, and other biological processes involved in colon cancer (9). We need more research to discover whether MIRNA plays an important role in the formation of MSI-H CRC.…”