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Altered MicroRNA Expression in Cervical Carcinomas

Authors' Affiliations: ¹ Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea and ² Department of Biochemistry, Hanyang University and GenoCheck Co. Ltd., Gyeonggi-do, Korea

Requests for reprints: Duk-Soo Bae or Byoung-Gie Kim, Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea. Phone: 82-2-3410-3519/3513; Fax: 82-2-3410-0630; E-mail: huna0{at}naver.com (D-S. Bae) or bksong.kim{at}samsung.com (B-G. Kim).

Purpose: MicroRNAs (miRNA) are small noncoding RNAs that are 18 to 25 nucleotides in length; they regulate the stability or translational efficiency of target mRNAs. Emerging evidence suggests that miRNAs might be involved in the pathogenesis of a variety of human cancers.

Experimental Design: In this study, we profiled miRNA expression in 10 early stage invasive squamous cell carcinomas (ISCC) and 10 normal cervical squamous epithelial specimens using TaqMan real-time quantitative PCR array methods. In order to evaluate the role of miR-199a, one of the most significantly overexpressed in ISCCs, we transfected cervical cancer cells (SiHa and ME-180) with anti–miR-199a oligonucleotides and assessed the cell viability.

Results: We found 70 genes (68 up-regulated, 2 down-regulated) with significantly different expression in the ISCCs compared with normal samples (P < 0.05). When we analyzed the expression of the 10 most significant miRNAs in 31 ISCCs, increased miR-127 expression was significantly associated with lymph node metastasis (P = 0.006). Transfection of anti–miR-199a oligonucleotides to cervical cancer cells suppressed cell growth in vitro, which was potentiated with the anticancer agent cisplatin.

Conclusions: Our results show that miRNA deregulation may play an important role in the malignant transformation of cervical squamous cells. In addition, they may offer new candidate targets to be exploited for both prognostic and therapeutic strategies in patients with cervical cancer.