MicroRNA-21 regulates proliferation and invasion in esophageal squamous cell carcinoma Purpose: MicroRNAs (miRNAs) are ~22 nucleotide non-coding RNA molecules that regulate gene expression post-transcriptionally. Aberrant expression of miRNAs in various human cancers suggests a role for miRNAs in tumorigenesis. It is reported that miR-21 is overexpressed in a wide variety of cancers and has been reported causally linked to cellular proliferation, invasion, and apoptosis by targeting the tumor suppressor protein programmed cell death 4 (PDCD4). The aim of this study was (1) to determine a role of microRNA-21 (miR-21) in esophageal squamous cell carcinoma (ESCC), (2) to elucidate the regulation of the programmed cell death 4 (PDCD4) gene by miR-21. Experimental Design: miR-21 expression was investigated in 20 matched normal esophageal epitheliums and ESCCs and 7 ESCC cell lines (TE6, TE8, TE10, TE11, TE12, TE14, KYSE30) by TaqMan quantitative real-time-polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). To evaluate the role of miR-21, cell proliferation and invasion was analyzed with anti-miR-21 transfected cells. In addition, the regulation of PDCD4 by miR-21 was elucidated to identify the mechanisms of this regulation. Results: Of 20 paired samples, 18 cancer tissues overexpressed miR-21 in comparison to matched normal epitheliums. Specifically, patients with lymph node metastasis or venous invasion showed significantly high expression of miR-21. ISH for miR-21 showed strong positive staining in paraffin-embedded ESCC tissues. All 7 ESCC cell lines also overexpressed miR-21 and anti-miR-21 transfected cells showed significant reduction in cellular proliferation and invasion. The PDCD4-protein levels in ESCC cells have an inverse correlation with miR-21 expression. Anti-miR-21 transfected cells increased PDCD4-protein expression without changing the PDCD4-mRNA level and increased a luciferase-reporter activity containing the PDCD4-3\#8217;-UTR construct. Conclusions: MicroRNA-21 targets PDCD4 at the post-transcriptional level and regulates cell proliferation and invasion in ESCC. It may serve as a novel therapeutic target in ESCC.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2535.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

American Association for Cancer Research
2009