lncRNA CASC9 positively regulates CHK1 to promote breast cancer cell proliferation and survival through sponging the miR‑195/497 cluster

Shao, Guoli; Wang, Mengchuan; Fan, Xulong; Zhong, Lin; Wang, Zixiang; Zhang, Pusheng; Ji, Shufeng

doi:10.3892/ijo.2019.4734

Cited by 22 publications

(25 citation statements)

References 51 publications

(47 reference statements)

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“…LncRNA CASC9 facilitates glioma tumorigenesis by sponging miR-519d 30 . LncRNA CASC9 plays an oncogenic role in breast cancer by sponging the miR-195/497 cluster 31 . In this study, we first used bioinformatics tools to predict that CASC9 is predominantly localized to the cytoplasm of CRC cells, which was subsequently verified by a subcellular fractionation assay in CRC cells.…”

Section: Discussionmentioning

confidence: 99%

Silencing long non-coding RNA CASC9 inhibits colorectal cancer cell proliferation by acting as a competing endogenous RNA of miR-576-5p to regulate AKT3

et al. 2020

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Increasing studies have shown that long non-coding RNAs (lncRNAs) are regarded as important regulators in the occurrence and development of colorectal cancer (CRC). Although lncRNA CASC9 has been studied in CRC, the detailed regulatory mechanism of CASC9 in CRC is still unclear. In this study, we found that CASC9 was significantly upregulated in CRC tissues and cell lines compared to normal controls and that aberrant expression was associated with the tumor-node-metastasis (TNM) stage of CRC. Functionally, CASC9 depletion efficiently inhibited the proliferation of CRC cells and induced cell apoptosis in vitro. Mechanistically, CASC9 was mainly enriched in the cytoplasm of CRC cells and interacted directly with miR-576-5p. Downregulation of miR-576-5p reversed the inhibitory effect of CASC9 siRNA on CRC cell progression. Furthermore, AKT3 has been identified as a downstream target of miR-576-5p. Spearman’s correlation analysis revealed that AKT3 was negatively correlated with miR-576-5p but positively correlated with CASC9. Downregulation of miR-576-5p restored the effect of CASC9 silencing on AKT3 expression. Therefore, silencing CASC9 could downregulate the expression of AKT3 by reducing the competitive binding of CASC9 to miR-576-5p, thus suppressing CRC cell proliferation and promoting cell apoptosis. In summary, we identified CASC9 as an oncogenic lncRNA in CRC and defined the CASC9/miR-576-5p/AKT3 axis, which might be considered a potential therapeutic target for CRC patients, as a novel molecular mechanism implicated in the proliferation and apoptosis of CRC.

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Section: Discussionmentioning

confidence: 99%

Silencing long non-coding RNA CASC9 inhibits colorectal cancer cell proliferation by acting as a competing endogenous RNA of miR-576-5p to regulate AKT3

et al. 2020

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“…31,32 Shao et al proved that lncRNA CASC9 may be used as a novel therapeutic target and as a potential diagnostic marker for BC. 33 Huang et al identified a panel of serum noncoding RNAs (ncRNAs) as potential diagnostic and prognostic biomarkers for BC that included the ncRNAs let-7a, miR-155, miR-574-5p, and MALAT1. 34 Based on our experiments, we found that exosomal H19 could effectively distinguish BC patients from BBD and NC subjects with a significantly high AUC value of 0.870 as well as a sensitivity of 87.0% and a specificity of 70.6%.…”

Section: Discussionmentioning

confidence: 99%

<p>Determination of Serum Exosomal H19 as a Noninvasive Biomarker for Breast Cancer Diagnosis</p>

Zhong¹,

Wang²,

Li³

et al. 2020

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Purpose: There is an urgent need for new biomarkers for the diagnosis of breast cancer. Exosomes can communicate with cells through transport molecules, including long-chain noncoding RNA (lncRNA), which is considered as a promising noninvasive biomarker. Here, we aimed to determine the potential of long noncoding RNA (lncRNA) H19 in the circulating exosomes for the diagnosis of breast cancer (BC). Materials and Methods: We measured the levels of lncRNA H19 in serum-derived exosomes from patients with breast cancer (BC) or benign breast disease (BBD) and healthy subjects, using quantitative real-time PCR. H19 levels were also measured for pre-operative and post-operative patients. Receiver operating characteristic curve was constructed, and the area under the curve (AUC) was calculated to determine the applicability of exosomal H19 levels as biomarkers in BC. The relationship between H19 relative expression and clinical features of BC patients was also analyzed. Results: Exosomal H19 expression levels were upregulated in patients with BC compared to that in patients with BBD and healthy controls (BC vs BBD, P < 0.001; BC vs healthy subjects, P < 0.001). The median serum exosomal H19 levels were significantly lower in post-operative than that in the pre-operative patients (P < 0.001). The AUC for exosomal H19 analysis was 0.870 (95% CI: 0.774-0.966) with a sensitivity of 87.0% and specificity of 70.6%, which was higher than the AUCs for CA15-3 and CEA, ie, 0.822 and 0.811, respectively. Moreover, exosomal H19 expression levels were associated with lymph node metastasis (P = 0.039), distant metastasis (P = 0.008), TNM stages (P = 0.022), ER (P=0.009), PR (P = 0.018), and Her-2 (P = 0.021). Conclusion: Our results indicated that serum exosomal H19 acts as a novel biomarker for the diagnosis of BC.

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“…4 lncRNAs act as signaling molecules, scaffolds, and instructors, and exert their influence at several levels including transcription, post-transcription, and translation. 5 In recent years, abundant evidence has revealed that anomalous expression of lncRNAs such as HOXD-AS1, H19, CASC9, and NORAD [6][7][8][9] may drive the pathogenesis of breast cancer. In addition, anomalous expression of lncRNAs may serve as a biomarker for breast cancer.…”

Section: Introductionmentioning

confidence: 99%

<p>lncRNA NEAT1 Facilitates Cell Proliferation, Invasion and Migration by Regulating CBX7 and RTCB in Breast Cancer</p>

Yan

Zhang

Yin

et al. 2020

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To investigate the association between the lncRNA NEAT1 and breast cancer, and to determine the influence of NEAT1 on regulation of other signaling molecules in breast cancer. Methods: In the present study, we measured levels of the lncRNA NEAT1 in 106 breast cancer patients and in a human breast cancer cell line by qRT-PCR. The correlation between NEAT1 expression and patients' clinical characteristics was analyzed with in-house and TCGA data. We used cellular functioning assays and cell immunofluorescence assay to evaluate the role of NEAT1 and its target molecules in proliferation, invasion and migration in breast cancer. We used Western blotting to explore possible targets of NEAT1 and a subcellular fractionation assay to locate NEAT1 expression. Results: NEAT1 was overexpressed in breast cancer tissue and also closely related to advanced clinical stages and positive lymph node metastases. NEAT1 levels were also tightly correlated to prognosis for breast cancer patients in survival analyses. Cellular function assays revealed that downregulation of NEAT1 could inhibit breast cancer cell viability, invasion and migration. Western blotting revealed down-regulation of CBX7 and upregulation of RTCB following NEAT1 inhibition. Based on the cytoplasmic and nuclear expression of NEAT1, we investigated the possible regulation of CBX7 and RTCB by NEAT1. Results showed that NEAT1 regulated the expression of CBX7 and RTCB, possibly by binding of NEAT1 to DNA in the nucleus, which facilitates cell proliferation, invasion and migration. Conclusion: The current results suggest that the lncRNA NEAT1 is upregulated in breast cancer and facilitates tumor cell viability, invasion and migration via CBX7 and RTCB.

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lncRNA CASC9 positively regulates CHK1 to promote breast cancer cell proliferation and survival through sponging the miR‑195/497 cluster

Cited by 22 publications

References 51 publications

Silencing long non-coding RNA CASC9 inhibits colorectal cancer cell proliferation by acting as a competing endogenous RNA of miR-576-5p to regulate AKT3

Silencing long non-coding RNA CASC9 inhibits colorectal cancer cell proliferation by acting as a competing endogenous RNA of miR-576-5p to regulate AKT3

<p>Determination of Serum Exosomal H19 as a Noninvasive Biomarker for Breast Cancer Diagnosis</p>

<p>lncRNA NEAT1 Facilitates Cell Proliferation, Invasion and Migration by Regulating CBX7 and RTCB in Breast Cancer</p>

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