Mature miR-184 as Potential Oncogenic microRNA of Squamous Cell Carcinoma of Tongue

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.

[1]  B. Cullen.  Transcription and processing of human microRNA precursors. , 2004, Molecular cell.

[2]  G. Hutvagner,et al.  A microRNA in a Multiple-Turnover RNAi Enzyme Complex , 2002, Science.

[3]  H. Müller,et al.  Circulating Nucleic Acids in Plasma or Serum (CNAPS) as Prognostic and Predictive Markers in Patients with Solid Neoplasias , 2005, Disease markers.

[4]  R. Lavker,et al.  MicroRNAs of the mammalian eye display distinct and overlapping tissue specificity. , 2006, Molecular vision.

[5]  C. Croce,et al.  MicroRNA signatures in human cancers , 2006, Nature Reviews Cancer.

[6]  William Ignace Wei,et al.  Prognostic factors of clinically stage I and II oral tongue carcinoma—A comparative study of stage, thickness, shape, growth pattern, invasive front malignancy grading, martinez‐gimeno score, and pathologic features , 2002, Head & neck.

[7]  Tushar Patel,et al.  Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. , 2006, Gastroenterology.

[8]  Shuomin Zhu,et al.  miR-21-mediated tumor growth , 2007, Oncogene.

[9]  Vishnu Swarup,et al.  Circulating (cell‐free) nucleic acids – A promising, non‐invasive tool for early detection of several human diseases , 2007, FEBS letters.

[10]  K. Kosik,et al.  MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. , 2005, Cancer research.

[11]  M. Fleischhacker,et al.  Circulating nucleic acids (CNAs) and cancer--a survey. , 2007, Biochimica et biophysica acta.

[12]  Phillip D Zamore,et al.  RNAi: nature abhors a double-strand. , 2002, Current opinion in genetics & development.

[13]  P. Yuen,et al.  Clinicopathological analysis of local spread of carcinoma of the tongue. , 1998, American journal of surgery.