Long non-coding RNA CASC2 regulates cell biological behaviour through the MAPK signalling pathway in hepatocellular carcinoma

Gan, Yuanyuan; Han, Ning; He, Xueling; Yu, Jiajun; Zhang, Meixia; Zhou, Yu‐Fu; Liang, Huiling; Deng, Junjian; Yang, Zheng; Ge, Wei; Zhou, Long; Xu, Ximing

doi:10.1177/1010428317706229

Cited by 34 publications

(33 citation statements)

References 26 publications

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“…The data suggested that these lncRNAs may participate in the tumorigenesis and development via regulating the cancer-related pathways in TNBC. Our data are in line with previous reports and provide a new therapeutic possibility for TNBC [45,46], but further experimental validation is needed .…”

Section: Discussionsupporting

confidence: 81%

Comprehensive Analysis of Differentially Expressed Profiles of lncRNAs/mRNAs and miRNAs with Associated ceRNA Networks in Triple-Negative Breast Cancer

Yang

Liu

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Triple-negative breast cancer (TNBC) is a subtype of highly malignant breast cancer with poor prognosis. Growing evidence indicates that Long noncoding RNAs (lncRNAs) play important regulatory roles in the development and progression of a variety of cancers including breast cancer. However, the underlying mechanisms remain largely unknown. Methods: Here, we compared the expression profiles of mRNAs, lncRNAs and miRNAs between 111 TNBC tissues and 104 non-cancerous tissues utilizing RNA-Seq Data from The Cancer Genome Atlas (TCGA). Gene Ontology and KEGG pathway enrichment analyses were executed to investigate the principal functions of the significantly dysregulated mRNAs. Moreover, Kaplan-Meier survival analyses were performed to determine the effects of differentially expressed lncRNAs/mRNAs/miRNAs on overall survival. Subsequently, we constructed a competing endogenous RNA (ceRNA) network, which included 66 dysregulated lncRNAs, 24 miRNAs and 55 mRNAs. The four dysregulated lncRNAs, three aberrantly expressed miRNAs and four mRNAs were confirmed in the ceRNA network by qRT-PCR in 30 pairs of samples, respectively. Results: A total of 1441 lncRNAs, 114 miRNA and 2501 mRNAs were found to be differentially expressed in TNBC tissues compared with controls. 109 lncRNAs and 124 mRNAs might serve as prognostic signature for patients with TNBC according to the survival analysis. Functional analysis revealed that 19 mRNAs in the ceRNA network were enriched in 17 cancer-related pathways. Conclusion: Taken together, we identified novel lncRNAs/miRNAs which may serve as potential biomarkers to predict the survival and therapeutic targets for TNBC patients based on a large-scale sample. More importantly, we constructed the ceRNA network of TNBC, which provides valuable information to further explore the molecular mechanism underlying tumorigenesis and development of TNBC.

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Section: Discussionsupporting

confidence: 81%

Comprehensive Analysis of Differentially Expressed Profiles of lncRNAs/mRNAs and miRNAs with Associated ceRNA Networks in Triple-Negative Breast Cancer

Yang

Liu

Wang

et al. 2018

Cell Physiol Biochem

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“…Cancer susceptibility candidate 2 (CASC2) is a lncRNA located on chromosome 10q26 that was discovered by Baldinu et al () in the context of endometrial cancer. It has since been shown to play a role in regulating the progression and growth of a number of cancers, including colorectal (Huang et al, ), lung (He et al, ), and hepatocellular (Gan et al, ), among others (Baldinu et al, ; Cao et al, ; Li, Xue, Feng, & Mao, ; Wang et al, ). CASC2 acts through microRNAs (miRNAs) (Huang et al, ; Wang et al, ), as well as through the Wnt/β‐catenin (Pei et al, ), MAPK (Gan et al, ; Li et al, ), and NF‐κB signaling pathways (Ni et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…It has since been shown to play a role in regulating the progression and growth of a number of cancers, including colorectal (Huang et al, ), lung (He et al, ), and hepatocellular (Gan et al, ), among others (Baldinu et al, ; Cao et al, ; Li, Xue, Feng, & Mao, ; Wang et al, ). CASC2 acts through microRNAs (miRNAs) (Huang et al, ; Wang et al, ), as well as through the Wnt/β‐catenin (Pei et al, ), MAPK (Gan et al, ; Li et al, ), and NF‐κB signaling pathways (Ni et al, ). Even though recent research (Gan et al, ) has suggested a mechanism for CASC2 activity in HCC, characterizing the effects of CASC2 on HCC growth and progression with even greater specificity promises to improve our HCC treatment capabilities.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA CASC2 regulates hepatocellular carcinoma cell oncogenesis through miR‐362‐5p/Nf‐κB axis

Zhao

Zhang

2018

Journal Cellular Physiology

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The long non-coding RNA segment cancer susceptibility candidate 2 (CASC2) has been shown to suppress tumor growth in a variety of cancers, including hepatocellular carcinoma (HCC). However, the mechanism by which CASC2 exerts control over HCC has yet to be established. In the present study, we first demonstrated that CASC2 is downregulated in human HCC tissues and HCC cell lines as compared to adjacent non-tumor tissues (NTTs) and a liver cell line, respectively. After finding that CASC2 knockdown significantly promotes HCC cells migration and invasion as well as that CASC2 overexpression inhibits cell migration and invasion, we identified the microRNA miR-362-5p as an endogenous target of CASC2. Through the use of wild type and mutant CASC2 binding sites inserted into psiCHECK-2 luciferase reporter plasmids, as well as qRT-PCR, we determined that CASC2 overexpression reduces miR-362-5p expression levels, while inhibiting CASC2 activity increases miR-362-5p expression. Past research has shown that miR-362-5p stimulates the NF-κB pathway, which has been implicated in the survival and proliferation of a variety of cancer cells. We therefore investigated the effects of CASC2 expression on NF-κB pathway activity. Ultimately, we determined that CASC2 regulates HCC cell activity by targeting miR-362-5p and thus inhibiting the NF-κB pathway. The present study not only identifies CASC2 as an important HCC cell regulator, but also suggests its mechanism of action. It therefore provides the basis for designing strategies to target CASC2 activity and thereby inhibit HCC growth and progression.

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“…For example, in esophageal carcinoma, CASC2 was shown to be an oncogene suppressor through inhibition of the NF-κB pathway [29] or that it acted as a ceRNA of miR-18a-5p to exert its biological effects by modulating the expression of PTEN [30]. In hepatocellular carcinoma, lncRNA CASC2 may regulate cell biological behavior through the MAPK signaling pathway [17]. Additionally, it suppressed the epithelial-mesenchymal transition of hepatocellular carcinoma cells through the CASC2/ miR-367/FBXW7 axis [24].…”

Section: Discussionmentioning

confidence: 99%

“…Now increasing numbers of studies have shown that CASC2 is also significantly downregulated in other cancers, such as hepatocellular carcinoma, colorectal cancer, and bladder cancer [17-19], and it could act as a tumor suppressor with implications for diagnosis and therapy [20]. Numerous researchers have reported that CASC2 is implicated in tumor initiation and progression and has shown a potential for predicting cancer prognosis [21-23].…”

Section: Introductionmentioning

confidence: 99%

Low Expression of LncRNA Cancer Susceptibility Candidate 2 and its Clinical Significance in Cancer Tissues

Zhu

Liu

Chen

2018

Cell Physiol Biochem

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Background/Aims: Long noncoding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) is downregulated in various cancers and involved in both tumorigenesis and progression. The aim of this study was to assess the prognostic value of lncRNA CASC2 in cancer patients. Methods: We searched the Web of Science, PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and the Wanfang database to identify studies evaluating the prognostic value of lncRNA CASC2 in cancer patients. Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed-effects/random-effects models. Results: A total of eight studies were included. The combined results showed that lncRNA CASC2 was significantly associated with decreased overall survival (OS) (HR = 0.37, 95% CI, 0.27–0.46, P < 0.001). Subgroup analyses further indicated that low expression of lncRNA CASC2 predicted decreased OS in cancer patients. Additionally, low CASC2 expression levels in cancer tissues appeared to be correlated with advanced clinical staging (OR = 3.32, 95% CI, 2.29–4.80, P < 0.001). Conclusions: Low CASC2 expression appears to be predictive of poor OS and advanced tumor stage in multiple cancers. CASC2 expression may serve as unfavorable prognostic factor for clinical outcomes in cancer patients.

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Long non-coding RNA CASC2 regulates cell biological behaviour through the MAPK signalling pathway in hepatocellular carcinoma

Cited by 34 publications

References 26 publications

Comprehensive Analysis of Differentially Expressed Profiles of lncRNAs/mRNAs and miRNAs with Associated ceRNA Networks in Triple-Negative Breast Cancer

Comprehensive Analysis of Differentially Expressed Profiles of lncRNAs/mRNAs and miRNAs with Associated ceRNA Networks in Triple-Negative Breast Cancer

Long noncoding RNA CASC2 regulates hepatocellular carcinoma cell oncogenesis through miR‐362‐5p/Nf‐κB axis

Low Expression of LncRNA Cancer Susceptibility Candidate 2 and its Clinical Significance in Cancer Tissues

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