CRNDE, a long non-coding RNA responsive to insulin/IGF signaling, regulates genes involved in central metabolism.

Colorectal neoplasia differentially expressed (CRNDE) is a novel gene that is activated early in colorectal cancer but whose regulation and functions are unknown. CRNDE transcripts are recognized as long non-coding RNAs (lncRNAs), which potentially interact with chromatin-modifying complexes to regulate gene expression via epigenetic changes. Complex alternative splicing results in numerous transcripts from this gene, and we have identified novel transcripts containing a highly-conserved sequence within intron 4 ("gVC-In4"). In colorectal cancer cells, we demonstrate that treatment with insulin and insulin-like growth factors (IGF) repressed CRNDE nuclear transcripts, including those encompassing gVC-In4. These repressive effects were negated by use of inhibitors against either the PI3K/Akt/mTOR pathway or Raf/MAPK pathway, suggesting CRNDE is a downstream target of both signaling cascades. Expression array analyses revealed that siRNA-mediated knockdown of gVC-In4 transcripts affected the expression of many genes, which showed correlation with insulin/IGF signaling pathway components and responses, including glucose and lipid metabolism. Some of the genes are identical to those affected by insulin treatment in the same cell line. The results suggest that CRNDE expression promotes the metabolic changes by which cancer cells switch to aerobic glycolysis (Warburg effect). This is the first report of a lncRNA regulated by insulin/IGFs, and our findings indicate a role for CRNDE nuclear transcripts in regulating cellular metabolism which may correlate with their upregulation in colorectal cancer.

Ellis BC ，Graham LD ，Molloy PL 《-》

CRNDE, a long-noncoding RNA, promotes glioma cell growth and invasion through mTOR signaling.

The transcripts of the gene Colorectal Neoplasia Differentially Expressed (CRNDE) are recognized as long-noncoding RNAs (lncRNAs), which are expressed in specific regions within the human brain, and are the most upregulated lncRNA in gliomas. However, the underlying regulation and function of CRNDE in gliomas are largely unknown. In this study, the upregulation of CRNDE was confirmed in both primary specimens from glioma patients and in vitro with cell lines. Overexpression of specific CRNDE transcript promotes cell growth and migration in vitro while knockdown of CRNDE expression manifests a repressive function during these cellular processes. The growth promoting effect of CRNDE was also demonstrated in a xenograft mouse model. Mechanistic studies further revealed that histone acetylation in the promoter region might account for the upregulation of CRNDE, and the level of CRNDE expression could be modulated by mammalian Target of Rapamycin (mTOR) signaling in glioma. Thus, our results shed a light on utilizing CRNDE as a potential novel therapeutic target for the treatment of glioma.

Wang Y ，Wang Y ，Li J ，Zhang Y ，Yin H ，Han B ... -  《-》

Highly expressed long non-coding RNA CRNDE promotes cell proliferation through PI3K/AKT signalling in non-small cell lung carcinoma.

Recently, numerous studies have revealed that long non-coding RNAs (lncRNAs) play complex roles in various lung diseases, while the colorectal neoplasia differentially expressed (CRNDE) functions in non-small cell lung carcinomas (NSCLC) remain largely unknown. In the present study, we investigate the role and mechanism of CRNDE in the progression of NSCLC. The mRNA level of CRNDE in NSCLC patients and cells was detected by qRT-PCR. The influence of CRNDE silencing or over-expression on NSCLC cell proliferation and growth were assessed by MTT and flow cytometry, respectively. We also investigated the effect of abnormal CRNDE expression on cyclins and PI3K/AKT pathway. Furthermore, si-CRNDE NSCLC cell lines were injected subcutaneously into nude mice to explore tumour formation in vivo. The expression of CRNDE was significantly upregulated in NSCLC patients and cells. In addition, both loss and gain function assays revealed that CRNDE promoted NSCLC cell proliferation and growth both in vitro and in vivo. Moreover, CRNDE regulated the cell cycle transition from G0 /G1 stage to S stage and modulated the expression of CDK4, CDK6 and CCNE1. We further illustrated that CRNDE activated PI3K/AKT signalling in NSCLC cell lines. In conclusion, CRNDE was highly expressed in NSCLC malignant tissues and the heightened CRNDE strongly promoted NSCLC cell proliferation and growth through activating PI3K/AKT signalling; our results shed a light on utilizing CRNDE as a potential novel therapeutic target for the treatment of NSCLC.

Liu XX ，Xiong HP ，Huang JS ，Qi K ，Xu JJ ... -  《-》

Long noncoding RNA CRNDE stabilized by hnRNPUL2 accelerates cell proliferation and migration in colorectal carcinoma via activating Ras/MAPK signaling pathways.

Jiang H ，Wang Y ，Ai M ，Wang H ，Duan Z ，Wang H ，Zhao L ，Yu J ，Ding Y ，Wang S ... -  《Cell Death & Disease》

The lncRNA CRNDE promotes colorectal cancer cell proliferation and chemoresistance via miR-181a-5p-mediated regulation of Wnt/β-catenin signaling.

Han P ，Li JW ，Zhang BM ，Lv JC ，Li YM ，Gu XY ，Yu ZW ，Jia YH ，Bai XF ，Li L ，Liu YL ，Cui BB ... -  《Molecular Cancer》