Long-Noncoding RNA Colorectal Neoplasia Differentially Expressed Gene as a Potential Target to Upregulate the Expression of IRX5 by miR-136-5P to Promote Oncogenic Properties in Hepatocellular Carcinoma

Abstract

Background/Aims: The long-noncoding RNA colorectal neoplasia differentially expressed (CRNDE) gene was first found to be activated in colorectal neoplasia. Now, it also has been found to be upregulated in many other solid tumors. Whether CRNDE affects tumorigenesis remains unknown. Methods: We conducted bioinformatics, real-time polymerase chain reaction (PCR), Western blot analysis, cell proliferation assay, colony formation assay, wound healing assay, cell migration and invasion assays, RNA immunoprecipitation, and reporter vector construction and luciferase assays. Results: CRNDE was upregulated in hepatocellular carcinoma (HCC). The overexpression of CRNDE promoted HCC cellular proliferation, migration, and invasion in intro and in vivo, and acted as an oncogene in HCC progression. Furthermore, CRNDE impaired miR-136-5P expression in a RISC manner, and a reciprocal repression feedback loop was possible between CRNDE and miR-136-5P. We found that the neighboring mRNA of CRNDE was IRX5, and IRX5 increased the tumorigenicity of HCC cells. IRX5 was a potential downstream target gene of miR-136-5P. MiR-136 regulated IRX5 by interacting with its 3’UTR. In addition, miR-136-5P was involved in the CRNDE-regulated expression of IRX5. Conclusion: CRNDE acted as a tumor oncogene by exhibiting oncogenic properties of human HCC and revealed a novel CRNDE-miR-136-5P-IRX5 regulatory network in HCC. CRNDE may be considered to be a potential target for HCC therapies based on its ability to upregulate IRX5, and it deserves further investigation.

The long non-coding RNA CRNDE regulates growth of multiple myeloma cells via an effect on IL6 signalling

“…In particular, it has recently been reported that CRNDE controls proliferation and survival of the U266 MM cell line by acting as a molecular sponge for miR-451 [29]. Further, another microRNA, miR-136-5p, which is observed to be sponged by CRNDE in several tumours [49,[54][55][56] has been reported to target the IL6R transcript in rat microglial cells [57]. However, miR-451 and miR-136-5p were not detectable by real time RT-PCR in either wild type or CRNDE Δ/Δ KMS11 cells, or in the NC1 CRISPRi cell lines used in the current study (data not shown), indicating that the effects of CRNDE in these models was not mediated via these miR-NAs.…”

LncRNA FAM83H-AS1 promotes triple-negative breast cancer progression by regulating the miR-136-5p/metadherin axis

“…Interestingly, miR-136-5p was identified as a potential target for FAM83H-AS1; this was further confirmed by qRT-PCR, luciferase activity, and the RIP assays. MiR-136-5p was found to inhibit cell proliferation, migration and invasion in renal cell carcinoma [34], liver cancer -by regulating IRX5 [35], and in colon cancer, through targeting LRH-1/Wnt signaling [36]. MiR-136 also inhibits cell survival, proliferation, cancer stem cell spheroid formation, and tumor angiogenesis in paclitaxel-resistant ovarian cancer cells by targeting Notch3 [37].…”

The role of long non‐coding RNAs in multiple myeloma

“…The altered expression of CRNDE is observed in many types of cancers, including hepatocellular carcinoma and acute myeloid leukemia (AML). [76][77][78] Le Dieu et al reported that there was a dramatic increase in CRNDE in both CD4(+) and CD8(+) cells in AML patients, which indicates that loss of CRND expression may be associated with the transition to a single-positive stage. 78 Keller et al also found that CRNDE involves cellular differentiation.…”