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.

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. 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. 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. 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.

Zhu L ，Liu Y ，Chen Q ，Yu G ，Chen J ，Chen K ，Yang N ，Zeng T ，Yan S ，Huang A ，Tang H ... -  《-》

Long Non-Coding MALAT1 Functions as a Competing Endogenous RNA to Regulate Vimentin Expression by Sponging miR-30a-5p in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) has a high morbidity as well as mortality and is believed to be one of the most prevalent cancers worldwide. The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is involved in numerous cancers, including HCC. This study aimed to explore the role of MALAT1 in HCC progression. The expression levels of MALAT1 and Vimentin in HCC tissues and relative pair-matched adjacent normal liver tissues were analyzed by RT-PCR, and immunohistochemistry. Using bioinformatics analysis and dual-luciferase assay, we examined the correlation between MALAT1 and miR-30a-5p. Dual-luciferase assay and western blotting suggested that Vimentin was a target of miR-30a-5p. A wound healing assay and transwell assays were employed to determine the effect of MALAT1 and miR-30a-5p on cell migration and invasion in HCC. Our data demonstrated that the levels of MALAT1 and Vimentin were upregulated in HCC tissues and that miR-30a-5p was a direct target of MALAT1. Silenced MALAT1 and overexpressed miR-30a-5p each inhibited cell migration and invasion. Additionally, dual-luciferase assay and western blotting demonstrated that MALAT1 could competitively sponge miR-30a-5p and thereby regulate Vimentin. Our data suggest that MALAT1 acts as an oncogenic lncRNA that promotes HCC migration and invasion. Therefore, the MALAT1-miR-30a-5p-Vimentin axis is a potential therapeutic target and molecular biomarker in HCC.

Pan Y ，Tong S ，Cui R ，Fan J ，Liu C ，Lin Y ，Tang J ，Xie H ，Lin P ，Zheng T ，Yu X ... -  《-》

Long non-coding RNA CRNDE promotes malignant progression of hepatocellular carcinoma through the miR-33a-5p/CDK6 axis.

Lin C ，Xiang Y ，Sheng J ，Liu S ，Cui M ，Zhang X ... -  《-》

lncRNA CRNDE promotes the proliferation and metastasis by acting as sponge miR-539-5p to regulate POU2F1 expression in HCC.

Li Z ，Wu G ，Li J ，Wang Y ，Ju X ，Jiang W ... -  《BMC CANCER》

LncRNA CRNDE promotes hepatocellular carcinoma progression by upregulating SIX1 through modulating miR-337-3p.

Long noncoding RNA (lncRNA) is emerging as a vital regulator in various cancers. Recently, it was found that lncRNA colorectal neoplasia differentially expressed (CRNDE) plays an oncogenic role, promoting cell proliferation and migration in hepatocellular carcinoma (HCC). However, the underlying regulatory mechanism of lncRNA CRNDE remains unclear. The expression levels of lncRNA CRNDE and miR-337-3p were analyzed by real-time polymerase chain reaction, and sineoculis homeobox homolog 1 (SIX1) expression was determined by Western blot analysis. RNA pull-down, luciferase and Western blot analysis assays were used to examine the target relationship between lncRNA CRNDE and miR-337-3p as well as between miR-337-3p and SIX1. The functional effects of lncRNA CRNDE and miR-337-3p were examined in vitro by using cell viability, colony formation, wound scratch, transwell assays, and in vivo in a xenograft tumor mouse model. LncRNA CRNDE was overexpressed in tumor tissues of patients with HCC. LncRNA CRNDE downregulation significantly suppressed cell proliferation and migration. Mechanistic investigations demonstrated that lncRNA CRNDE interacted with miR-337-3p and decreased its expression, thereby increasing the protein expression of miR-337-3p's target, SIX1. In addition, in vivo experiments using a xenograft tumor mouse model revealed that lncRNA CRNDE served as an oncogene, partly through sponging miR-337-3p and upregulating SIX1 in HCC. In this study, we report a newly identified regulatory mechanism lncRNA CRNDE/miR-337-3p/SIX1 axis, suggesting a promising therapeutic target in HCC.

Tang D ，Zhao L ，Peng C ，Ran K ，Mu R ，Ao Y ... -  《-》