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Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
The long noncoding RNA CASC2 functions as a competing endogenous RNA by sponging miR-18a in colorectal cancer
Guanli Huang1, Xiaoli Wu2, Shi Li3
1Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China.
Abstract:
Recent evidence highlights the crucial regulatory roles of long noncoding RNAs (lncRNA) in tumor biology. In colorectal cancer (CRC), the expression of several lncRNAs is dysregulated and play essential roles in CRC tumorigenesis. However, the potential biological roles and regulatory mechanisms of the novel human lncRNA, CASC2 (cancer susceptibility candidate 2), in tumor biology are poorly understood. In this study, CASC2 expression was significantly decreased in CRC tissues and CRC cell lines, and decreased expression was significantly more frequent in patients with advanced tumor-node-metastasis stage disease (TNM III and IV) (P = 0.028). Further functional experiments indicate that CASC2 could directly upregulate PIAS3 expression by functioning as a competing endogenous RNA (ceRNA) for miR-18a. This interactions leads to the de-repression of genes downstream of STAT3 and consequentially inhibition of CRC cell proliferation and tumor growth in vitro and in vivo by extending the G0/G1-S phase transition. Taken together, these observations suggest CASC2 as a ceRNA plays an important role in CRC pathogenesis and may serve as a potential target for cancer diagnosis and treatment.
Insights
The long noncoding RNA CASC2 is downregulated in colorectal cancer (CRC) and inhibits tumor growth by regulating the PIAS3/STAT3 pathway. CASC2 acts as a competing endogenous RNA (ceRNA) and may be a therapeutic target for CRC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long noncoding RNAs (lncRNAs) are critical regulators in tumor biology.
- Dysregulated lncRNA expression is implicated in colorectal cancer (CRC) tumorigenesis.
- The role of the novel lncRNA CASC2 (cancer susceptibility candidate 2) in CRC remains unclear.
Purpose of the Study:
- To investigate the biological roles and regulatory mechanisms of CASC2 in colorectal cancer.
- To determine the expression levels and clinical significance of CASC2 in CRC patients.
Main Methods:
- Quantitative real-time PCR to assess CASC2 expression in CRC tissues and cell lines.
- Functional assays (in vitro and in vivo) to evaluate CASC2's impact on CRC cell proliferation and tumor growth.
- Mechanism studies involving RNA immunoprecipitation and luciferase reporter assays to elucidate CASC2's interaction with miR-18a and PIAS3.
Main Results:
- CASC2 expression was significantly decreased in CRC tissues and cell lines, correlating with advanced TNM stage.
- CASC2 functions as a competing endogenous RNA (ceRNA) by sponging miR-18a, leading to PIAS3 upregulation.
- CASC2 overexpression inhibited CRC cell proliferation and tumor growth by promoting G0/G1-S phase arrest via the STAT3 pathway.
Conclusions:
- CASC2 plays a tumor-suppressive role in colorectal cancer pathogenesis.
- The CASC2/miR-18a/PIAS3/STAT3 axis represents a novel regulatory mechanism in CRC.
- CASC2 holds potential as a diagnostic biomarker and therapeutic target for colorectal cancer.
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