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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
Mature miR-184 as Potential Oncogenic microRNA of Squamous Cell Carcinoma of Tongue
Thian-Sze Wong1, Xiao-Bing Liu, Birgitta Yee-Hang Wong
1Department of Surgery, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR China. thiansze@graduate.hku.hk
Purpose:
The aim of this study was to evaluate the microRNA expression patterns in squamous cell carcinoma (SCC) of the tongue.
Experimental Design:
Expression levels of 156 human mature microRNAs were examined using real-time quantitative PCR (Taq Man MicroRNA Assays; Human Panel) on laser microdissected cells of 4 tongue carcinomas and paired normal tissues. Expression of mature miR-184 was further validated in 20 paired tongue SCC and the normal tissues. Potential oncogenic functions of miR-184 were evaluated in tongue SCC cell lines (Cal27, HN21B, and HN96) with miR-184 inhibitor. Plasma miR-184 levels were evaluated using real-time quantitative PCR.
Results:
Using 3-fold expression difference as a cutoff level, we identified 24 up-regulated mature miRNAs including miR-184, miR-34c, miR-137, miR-372, miR-124a, miR-21, miR-124b, miR-31, miR-128a, miR-34b, miR-154, miR-197, miR-132, miR-147, miR-325, miR-181c, miR-198, miR-155, miR-30a-3p, miR-338, miR-17-5p, miR-104, miR-134, and miR-213; and 13 down-regulated mature miRNAs including miR-133a, miR-99a, miR-194, miR-133b, miR-219, miR-100, miR-125b, miR-26b, miR-138, miR-149, miR-195, miR-107, and miR-139. Overexpression of miR-184 was further validated in 20 paired tongue SCC and normal tissues (P = 0.002). Inhibition of miR-184 in tongue SCC cell lines could reduce cell proliferation rate. Down-regulation of c-Myc was observed in two cell lines in response to miR-184 inhibitor. Suppressing miR-184 could induce apoptosis in all three cell lines. Plasma miR-184 levels were significantly higher in tongue SCC patients in comparison with normal individuals, and the levels were significantly reduced after surgical removal of the primary tumors.
Conclusions:
Overexpression of miR-184 might play an oncogenic role in the antiapoptotic and proliferative processes of tongue SCC. In addition, plasma miR-184 levels were associated with the presence of primary tumor. Further studies on the aberrantly expressed miRNAs in tongue SCC as well as using plasma miRNAs as novel tumor markers are warranted.
Insights
MicroRNA-184 (miR-184) is overexpressed in tongue squamous cell carcinoma (SCC) and promotes cell proliferation and survival. Plasma miR-184 levels correlate with tumor presence, suggesting its potential as a diagnostic marker.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Squamous cell carcinoma (SCC) of the tongue is a significant health concern.
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are implicated in various cancers.
- Understanding miRNA expression patterns in tongue SCC is crucial for identifying potential diagnostic markers and therapeutic targets.
Purpose of the Study:
- To investigate the differential expression profiles of microRNAs in tongue squamous cell carcinoma (SCC) compared to normal tissues.
- To evaluate the functional role of specific overexpressed microRNAs, particularly miR-184, in tongue SCC.
- To assess the potential of plasma miR-184 as a non-invasive biomarker for tongue SCC.
Main Methods:
- Real-time quantitative PCR was employed to analyze the expression of 156 mature microRNAs in laser microdissected tongue SCC and paired normal tissues.
- miR-184 expression was further validated in a larger cohort, and its functional significance was assessed in tongue SCC cell lines using miR-184 inhibitors.
- Plasma miR-184 levels were quantified using real-time quantitative PCR in patients with tongue SCC and healthy controls.
Main Results:
- A total of 24 miRNAs were found to be up-regulated, and 13 were down-regulated in tongue SCC tissues.
- Overexpression of miR-184 was consistently observed in tongue SCC tissues (P = 0.002).
- Inhibition of miR-184 in tongue SCC cell lines reduced cell proliferation, induced apoptosis, and led to down-regulation of c-Myc. Plasma miR-184 levels were significantly elevated in patients with tongue SCC and decreased post-surgery.
Conclusions:
- miR-184 exhibits oncogenic properties in tongue SCC by promoting proliferation and inhibiting apoptosis.
- Plasma miR-184 levels serve as a potential indicator for the presence of primary tongue SCC.
- Further research into aberrant miRNA expression and the utility of plasma miRNAs as tumor markers in tongue SCC is warranted.
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