Long noncoding RNA CCAT2 promotes hepatocellular carcinoma proliferation and metastasis through up-regulation of NDRG1

Liu, Yuyang; Wang, Dan; Li, Yongguo; Yan, Shaoying; Yue, Huan; Ling, Jiaji; Chen, Fengjiao; Zhao, Yannan; Gou, Luxia; Tang, Ping; Huang, Aiping; Tang, Hua

doi:10.1016/j.yexcr.2019.03.029

Cited by 38 publications

(24 citation statements)

References 26 publications

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“…NDRG1 overexpression enhances aerobic glycolysis and imparts growth advantages to cells, induces the expression of hypoxia-associated genes, and causes lipid metabolism dysfunction in breast cancer (Sevinsky et al, 2018). A report revealed the role of the lncRNA CCAT2 in promoting cellular proliferation and metastasis through the upregulation of NDRG1 expression in HCC (Liu et al, 2019). Consistent with these results, we confirm that NDRG1 expression was upregulated in 20 pairs of HCC tissues and that patients with higher NDRG1 expression showed poorer clinical prognosis and histological grade.…”

Section: Discussionsupporting

confidence: 90%

LINC00844 promotes proliferation and migration of hepatocellular carcinoma by regulating NDRG1 expression

Wei

Huang

Zhang

et al. 2020

PeerJ

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Background Aberrant expression of long noncoding RNAs are implicated in the pathogenesis of human malignancies. LINC00844 expression is dramatically downregulated in prostate cancer, and functional studies have revealed the association between the aberrant expression of LINC00844 and prostate cancer cell invasion and metastasis. However, the function and mechanism of action of LINC00844 in the pathogenesis of hepatocellular carcinoma (HCC) are poorly understood. Methods LINC00844 and N-Myc downstream-regulated 1 (NDRG1) expression in HCC tissues and cell lines was detected with real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Correlations between LINC00844 expression level and clinicopathological features were investigated using the original data from The Cancer Genome Atlas (TCGA) database. HepG2 and HCCLM9 cell lines were transfected with Lv-LIN00844 virus to obtain LINC00844-overexpressing cell lines. Cell proliferation and cell invasion and migration were examined with the cell counting kit-8 (CCK-8) and transwell assay, respectively. Furthermore, the correlation between LINC00844 and NDRG1 expression was analysed using Pearson’s correlation analysis. Results LINC00844 expression was significantly downregulatedin HCC tissues and cell lines, and a statistical correlation was detected between low LINC00844 expression and sex (Female), advanced American Joint Committee on Cancer (AJCC) stage (III + IV), histological grade (G3 + G4), and vascular invasion (Micro and Macro). In vitro experiments showed that LINC00844 overexpression significantly repressed the proliferation, migration, and invasion of HCC cells. NDRG1 expression was higher in HCC tissues and LINC00844 could partly inhibit the expression of NDRG1.

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Section: Discussionsupporting

confidence: 90%

LINC00844 promotes proliferation and migration of hepatocellular carcinoma by regulating NDRG1 expression

Wei

Huang

Zhang

et al. 2020

PeerJ

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“…The role of lncRNAs in various biological processes, such as cell differentiation, proliferation and apoptosis in various diseases, including cancer, has received increasing attention (10)(11)(12). The colon cancer associated transcript 2 (CCAT2) gene has been reported to be upregulated in various types of human cancer, including gastric cancer, non-small cell lung cancer, esophageal cancer (13)(14)(15)(16)(17), hepatocellular carcinoma (18,19) and other tumors (20)(21)(22), and it is associated with the occurrence and metastasis of cancer, as well as poor prognosis. Previous studies have demonstrated that lncRNA CCAT2 is localized in the 8q24 genomic region, which has been identified as the first reproducible genetic risk site (23,24).…”

Section: Introductionmentioning

confidence: 99%

Long non‑coding RNA CCAT2 promotes prostate cancer cell proliferation and invasion by regulating the Wnt/β‑catenin signaling pathway

Xiong

Guo

et al. 2020

Oncol Lett

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Long non-coding RNA colon cancer associated transcript 2 (CCAT2) is dysregulated in a number of different types of human cancer, and affects cancer progression via the Wnt/β-catenin signaling pathway. However, the roles of CCAT2 and the Wnt/β-catenin signaling pathway in prostate cancer (PCa) are not completely understood. The present study aimed to investigate the potential mechanism of CCAT2 in PCa. In the present study, the reverse transcription-quantitative PCR (RT-qPCR) results indicated that CCAT2 expression was significantly upregulated in PCa tissues, and DU145 and PC3 cell lines compared with normal prostate tissues and the epithelial RWPE-1 cell line, respectively. Functional assays indicated that CCAT2 downregulation inhibited DU145 and PC3 cell proliferation, cell cycle, migration and invasion. In addition, the luciferase reporter assay, RT-qPCR and western blotting results indicated that CCAT2 regulated transcription factor 7 like 2 (TCF7L2) expression by binding to microRNA-217. Further western blotting and TOPFlash assays indicated that CCAT2-knockdown inhibited the Wnt/β-catenin signaling pathway in DU145 and PC3 cell lines by inhibiting the expression of TCF7L2. However, CCAT2-knockdown-mediated effects were reversed by the Wnt/β-catenin signaling pathway activator lithium chloride (LiCl). Further cell experiments suggested that LiCl treatment reversed CCAT2-knockdown-mediated inhibition of PCa cell proliferation, cell cycle, epithelial-mesenchymal transition, migration and invasion. Overall, the results indicated that CCAT2 regulated PCa via the Wnt/β-catenin signaling pathway; therefore, CCAT2 may exhibit key role during the progression of PCa and may serve as a therapeutic target for the disease.

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“…Even in HCC, the localization and functional mechanism of CCAT2 may differ among diverse HCC cell types. Liu et al (2019) demonstrated that CCAT2 positively regulated NDRG1 expression by enhancing its promoter activity in the nucleus in SMMC7721 and SK‐hep1 cells. However, CCAT2 was also been proved to function as a ceRNA through its interaction with miR‐34a in the cytoplasm of SMMC7721 cell (Chen, Bai, Li, Feng, & Wang, 2017).…”

Section: Discussionmentioning

confidence: 99%

CCAT2 contributes to hepatocellular carcinoma progression via inhibiting miR‐145 maturation to induce MDM2 expression

Niu

Wang

et al. 2020

Journal Cellular Physiology

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Long noncoding RNA colon cancer-associated transcript 2 (CCAT2) has been recently found to function as an oncogene in hepatocellular carcinoma (HCC).However, the mechanisms of CCAT2 in HCC development remain to be further explored. In the present study, we found that CCAT2 was abnormally upregulated in HCC cells and tissue specimens, exhibiting an inverse correlation with microRNA (miR)-145 expression. Mechanistic investigation showed that CCAT2 selectively blocked miR-145 processing, leading to decreased mature miR-145 presence. Both the in vitro and in vivo effects of CCAT2 knockdown on the proliferation and metastasis of HCC cells were reversed by miR-145 inhibitor, indicating that miR-145 modulation accounts for CCAT2-meditated HCC progression. Furthermore, miR-145 mimic dramatically suppressed HCC cells' proliferation and metastasis, revealing a tumor suppressor role of miR-145 in HCC. Mechanistically, MDM2 was predicted to be a potential target of miR-145. The luciferase and western blot assay demonstrated that miR-145 mimic largely inhibited MDM2 3′-untranslated region luciferase activity and MDM2 expression, followed by the upregulation of p53/p21 expression. Finally, the coexpression of MDM2 in miR-145 mimic-transfected HCC cells was able to largely compromise the inhibitory effects of miR-145 mimic on HCC cells' proliferation and metastasis in vitro and tumor formation in a xenograft model, confirming MDM2 is the critical mediator of miR-145 in HCC. In summary, our findings indicated that CCAT2 selectively blocks the miR-145 maturation process and plays an oncogene in HCC. Furthermore, a novel CCAT2/miR-145/MDM2 axis was revealed in HCC development and might provide a new target in the molecular treatment of HCC.

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Long noncoding RNA CCAT2 promotes hepatocellular carcinoma proliferation and metastasis through up-regulation of NDRG1

Cited by 38 publications

References 26 publications

LINC00844 promotes proliferation and migration of hepatocellular carcinoma by regulating NDRG1 expression

LINC00844 promotes proliferation and migration of hepatocellular carcinoma by regulating NDRG1 expression

Long non‑coding RNA CCAT2 promotes prostate cancer cell proliferation and invasion by regulating the Wnt/β‑catenin signaling pathway

CCAT2 contributes to hepatocellular carcinoma progression via inhibiting miR‐145 maturation to induce MDM2 expression

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Long noncoding RNA CCAT2 promotes hepatocellular carcinoma proliferation and metastasis through up-regulation of NDRG1

Cited by 38 publications

References 26 publications

LINC00844 promotes proliferation and migration of hepatocellular carcinoma by regulating NDRG1 expression

LINC00844 promotes proliferation and migration of hepatocellular carcinoma by regulating NDRG1 expression

Long non‑coding RNA CCAT2 promotes prostate cancer cell proliferation and invasion by regulating the Wnt/&beta;‑catenin signaling pathway

CCAT2 contributes to hepatocellular carcinoma progression via inhibiting miR‐145 maturation to induce MDM2 expression

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Long non‑coding RNA CCAT2 promotes prostate cancer cell proliferation and invasion by regulating the Wnt/β‑catenin signaling pathway