LncRNA CASC15 promotes colon cancer cell proliferation and metastasis by regulating the miR‑4310/LGR5/Wnt/β‑catenin signaling pathway

Jing, Niancai; Huang, Tao; Guo, Huaiyu; Yang, Jili; Li, Mingjing; Chen, Zhuo; Zhang, Yue

doi:10.3892/mmr.2018.9191

Cited by 43 publications

(41 citation statements)

References 42 publications

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“…3), thereby enhancing the proliferation and migration of NSCLC cells. In line with this, other groups have recently reported that CASC15 could promote tumorigenesis by activating Wnt//β-catenin signaling pathway in colon cancer and melanoma, suggesting that CASC15/β-catenin axis has an important and universal function in cancer development and progression [44,45].…”

Section: Discussionsupporting

confidence: 64%

Hypoxia-sensitive long noncoding RNA CASC15 promotes lung tumorigenesis by regulating the SOX4/β-catenin axis

Sun

Xiong

Jiang

et al. 2020

Preprint

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Background: Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are involved in the hypoxia-related cancer process and play pivotal roles in enabling malignant cells to survive under hypoxic stress. However, the molecular crosstalk between lncRNAs and hypoxia signaling cascades in non-small cell lung cancer (NSCLC) remains largely elusive.Methods: Firstly, we identified differentially expressed lncRNA cancer susceptibility candidate 15 (CASC15) as associated with NSCLC based on bioinformatic data. The clinical significance of CASC15 in lung cancer was investigated by Kaplan-Meier survival analysis. Then, we modulated CASC15 expression in NSCLC cell lines by RNAi. CCK-8 and transwell assays were carried out to examine the effects of CASC15 on proliferation and migration of NSCLC cells. Upstream activator and downstream targets of CASC15 were validated by luciferase reporter assay, qRT-PCR, Western blotting, and chromatin immunoprecipitation (ChIP). Lastly, RNA in situ hybridization (RNA-ISH) and immunohistochemistry (IHC) were performed to confirm the genetic relationships between CASC15 and related genes in clinical samples.Results: CASC15 was highly expressed in NSCLC tissues and closely associated with poor prognosis. Loss-of-function analysis demonstrated that CASC15 was essential for NSCLC cell migration and growth. Mechanistic study revealed that CASC15 was transcriptionally activated by hypoxia signaling in NSCLC cells. Further analysis showed that hypoxia-induced CASC15 transactivation was mainly dependent on hypoxia-inducible factor 1α (HIF-1α) and hypoxia response elements (HREs) located in CASC15 promoter. CASC15 promotes the expression of its chromosomally nearby gene, SOX4. Then SOX4 functions to stabilize β-catenin protein, thereby enhancing the proliferation and migration of NSCLC cells. HIF-1α/CASC15/SOX4/β-catenin pathway was activated in a substantial subset of NSCLC patients.Conclusions: HIF-1α/CASC15/SOX4/β-catenin axis plays an essential role in the development and progression of NSCLC. The present work provides new evidence that lncRNA CASC15 holds great promise to be used as novel biomarkers for NSCLC. Blocking the HIF-1α/CASC15/SOX4/β-catenin axis can serve as a potential therapeutic strategy for treating NSCLC.

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Section: Discussionsupporting

confidence: 64%

Hypoxia-sensitive long noncoding RNA CASC15 promotes lung tumorigenesis by regulating the SOX4/β-catenin axis

Sun

Xiong

Jiang

et al. 2020

Preprint

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“…Other studies have also con rmed that HULC can advance the proliferation of HCC cells and is positively related to the invasion of liver cancer cells [32]. LncRNA CASC15 has been found abnormally expressed in a variety of malignant tumors [33]. This study found that the expression level of CASC15 in HCC was increased.…”

Section: Discussionsupporting

confidence: 57%

Lnc-RNA CASC15 promotes HCC progression via modulation of Six1 targeted by miR-2355-5p

Han

Sui

Tao

et al. 2020

Preprint

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Background: Long-chain non-coding RNA (LncRNA) plays a key role in the biological processes of tumors. LncRNA CASC15 has been shown to be involved in the development of a variety of tumors. The study aimed to elucidate the mechanism of lncRNA CASC15 in the progression of hepatocellular carcinomas (HCC). Methods: qRT-PCR was used to detect the expression levels of CASC15, miR-2355-5p and Six1 mRNA in HCC tissues and cells. Six1 protein expression levels were detected by Western Blot. CCK-8 experiment, colony formation experiment, Edu staining and Transwell experiment analysis were used to analyze the effects of CASC15, miR-2355-5p and Six1 on cell proliferation, cell invasion and migration. The relationship between CASC15, miR-2355-5p and Six1 was analyzed using bioinformatics analysis and Luciferase. Result: CASC15 was raised in HCC tissues and HCC cells. Down-regulation of CASC15 inhibited the growth, migration, invasion and tumor growth of HCC cells. The expression level of miR-2355-5p was reduced in HCC tissues. In addition, miR-2355-5p inhibitor induced the growth, migration and invasion of HCC cells. MiR-2355-5p was predicted to be a downstream target of CASC15. The expression level of miR-2355-5p was negatively correlated with CASC15 in HCC tumor tissues. Six1 was predicted to be a downstream target of miR-30a-5p. In vitro and in vivo results showed that CASC15/miR-2355-5p can regulate Six1.Conclusion: LncCASC15 regulated the proliferation and invasion of Six1 by binding with miR-2355-5p in HCC, suggesting that CASC15 may be a potential target for HCC.

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“…In the current research, we discovered that silencing UNC5B-AS1 also repressed colon cancer HCT116 and Caco-2 cell migration and invasion, which illustrated that UNC5B-AS1 also engaged in the modulation of colon cancer metastasis and silencing UNC5B-AS1 could repress colon cancer metastasis. Moreover, in light of many other lncRNAs, such as lncRNA-activated by TGF-b (ATB) [25], lncRNA-cancer susceptibility 15 (CASC15) [26] and lncRNA-SUMO1P3 [27] also engaged in adjusting colon cancer growth and metastasis, we can put forward that colon cancer growth and metastasis are modulated by many lncRNAs that may from a very complicated regulatory network.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Silencing UNC5B antisense lncRNA 1 represses growth and metastasis of human Colon cancer cells via raising miR-622

Zhang

Lan

2019

Artificial Cells, Nanomedicine, and Biotechnology

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Background: Colon cancer is the most frequently lethal cancer in digestive system. Herein, we tested the influences of UNC5B antisense lncRNA 1 (UNC5B-AS1) on colon cancer cell growth and metastasis, along with the regulatory function of UNC5B-AS1 in microRNA-622 (miR-622) expression. Methods: Firstly, UNC5B-AS1 expression in colon cancer tissues and corresponding normal tissues were tested. Then, the influences of silencing UNC5B-AS1 by sh-UNC5B-AS1 transfection on colon cancer HCT116 and Caco-2 cell viability, proliferation, migration, invasion and apoptosis, as well as miR-622 expression were assessed, respectively. Subsequently, whether miR-622 attended to the influences of silencing UNC5B-AS1 on HCT116 and Caco-2 cells were probed. Finally, the activities of AMPK and PI3K/AKT pathways in cells were analysed. Results: UNC5B-AS1 had high expression level in colon cancer tissues. Silencing UNC5B-AS1 repressed HCT116 and Caco-2 cell proliferation, migration and invasion, but boosted cell apoptosis. Moreover, silencing UNC5B-AS1 raised miR-622 expression in HCT116 and Caco-2 cells. miR-622 inhibitor transfection weakened the influences of silencing UNC5B-AS1 on HCT116 and Caco-2 cells. Besides, Silencing UNC5B-AS1 suppressed AMPK and PI3K/AKT pathways via raising miR-622. Conclusion: Silencing UNC5B-AS1 repressed colon cancer growth and metastasis might be through raising miR-622 expression and suppressing AMPK and PI3K/AKT pathways.

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LncRNA CASC15 promotes colon cancer cell proliferation and metastasis by regulating the miR‑4310/LGR5/Wnt/β‑catenin signaling pathway

Cited by 43 publications

References 42 publications

Hypoxia-sensitive long noncoding RNA CASC15 promotes lung tumorigenesis by regulating the SOX4/β-catenin axis

Hypoxia-sensitive long noncoding RNA CASC15 promotes lung tumorigenesis by regulating the SOX4/β-catenin axis

Lnc-RNA CASC15 promotes HCC progression via modulation of Six1 targeted by miR-2355-5p

RETRACTED ARTICLE: Silencing UNC5B antisense lncRNA 1 represses growth and metastasis of human Colon cancer cells via raising miR-622

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