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Molecular Profiling of the Invasive Tumor Microenvironment in a 3-Dimensional Model of Colorectal Cancer Cells and Ex vivo Fibroblasts
Published on: April 29, 2014
miR-944 inhibits cell migration and invasion by targeting MACC1 in colorectal cancer
Liqiang Wen1, Yingru Li2, Zhipeng Jiang2
1Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, P.R. China.
Abstract:
Dysfunction of microRNAs (miRNAs) is strongly proved to participate in the pathogenesis and tumorigenicity of colorectal cancer (CRC). miR-944 was reported to play either oncogenic or tumor suppressive roles in human cancers. A recent study reported that the levels of miR-944 in recurrent CRC patients were evidently lower than that in non-recurrent cases, suggesting that miR-944 may function as a tumor suppressive miRNA in CRC. Yet, the clinical value and biological function of miR-944 remain rarely known in CRC. In the present study, we present that miR-944 level in CRC tissues is notably reduced compared to matched non-cancerous specimens. Its decreased level is evidently correlated with malignant clinical parameters and poor prognosis of CRC patients. Accordingly, the levels of miR-944 were obviously downregulated in CRC cells. Ectopic expression of miR-944 in CRC cells prominently inhibits the migration and invasion of tumor cells, while miR-944 knockdown increased these effects of CRC cells. Mechanically, miR-944 negatively regulated the metastasis-associated in colon cancer-1 (MACC1) abundance in CRC cells. Herein, MACC1 was found to be a downstream molecule of miR-944 in CRC. An inversely correlation between miR-944 and MACC1 was confirmed in CRC specimens. Furthermore, restoration of MACC1 expression could abrogate the anti-metastatic effects of miR-944 on CRC cells with enhanced cell migration and invasion. MACC1/Met/AKT signaling may be implicated with the function of miR-944 in CRC cells. Altogether, miR-944 potentially act as a prognostic predictor and a drug-target for CRC patients.
Insights
MicroRNA-944 (miR-944) is downregulated in colorectal cancer (CRC), inhibiting tumor cell migration and invasion. Lower miR-944 levels correlate with poor prognosis, suggesting its potential as a prognostic marker and therapeutic target for CRC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA (miRNA) dysfunction is implicated in colorectal cancer (CRC) pathogenesis.
- The specific role of miR-944 in CRC remains largely uncharacterized.
- Previous studies suggest miR-944 may act as a tumor suppressor in certain cancers.
Purpose of the Study:
- To investigate the clinical significance and biological function of miR-944 in colorectal cancer.
- To determine the correlation between miR-944 expression and clinicopathological features and prognosis in CRC patients.
- To elucidate the molecular mechanism underlying miR-944's function in CRC metastasis.
Main Methods:
- Quantitative real-time PCR to assess miR-944 levels in CRC tissues and cell lines.
- In vitro assays (migration, invasion) to evaluate the functional role of miR-944.
- Western blotting and correlation analysis to identify and validate miR-944 targets and pathways.
Main Results:
- miR-944 expression was significantly downregulated in CRC tissues and cells compared to non-cancerous controls.
- Reduced miR-944 levels correlated with advanced clinical parameters and poorer patient prognosis.
- Overexpression of miR-944 suppressed CRC cell migration and invasion, while knockdown enhanced these processes.
- miR-944 directly targets metastasis-associated in colon cancer-1 (MACC1), and MACC1/Met/AKT signaling is involved.
Conclusions:
- miR-944 functions as a tumor suppressor in colorectal cancer by inhibiting metastasis.
- miR-944 expression is a potential prognostic biomarker for CRC.
- Targeting miR-944 or its downstream effectors may offer a novel therapeutic strategy for CRC.
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