MicroRNA-22E Inhibits HER-3 Protein Expression to Facilitate Metastasis of Lung Adenocarcinomas
Hsin-Yuan Fang1, Tze-Yi Lin2, Shiow-Her Chiou3, Liang-Shun Wang4, Kuan-Chih Chow5*
1Departments of Surgery, School of Medicine, China Medical University, Taichung, Taiwan.
2Departments of Pathology, China Medical University Hospital, Taichung, Taiwan.
3Graduate Institute of Microbiology and Public Health, Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.
4Graduate Institution of Clinical Medicine, Medical College, Taipei Medical University, Section of Thoracic Surgery, Departments of Surgery, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan.
5Graduate Institute of Biomedical Sciences and Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.
DOI: 10.4236/jct.2015.64039   PDF   HTML   XML   2,733 Downloads   3,177 Views  

Abstract

MicroRNA-22 (miR-22), a short non-coding RNA that post-transcriptionally regulates mRNA stability and protein synthesis, has been shown to enhance metastatic potential and to suppress HER-3, an important mRNA marker for non-small cell lung cancer (NSCLC). However, the effect of miR-22 has not been investigated in lung adenocarcinoma (LADC), the most common type of NSCLC in the Far East. In this study, we analyzed the role of miR-22 expression in LADC patients. Expression of miR-22 was detected by reverse-transcription polymerase chain reaction (RT-PCR), and confirmed by cDNA sequencing. Signals of miR-22 in LADC sections were identified using in situ hybridization (ISH). The association between miR-22 expression and survival was evaluated by the log-rank test. Induction of miR-22 expression and the effect on HER-3 levels, as well as the subsequent cell behavior were also investigated In vitro. Two types of miR-22: miR-22 and miR-22H, were detected by RT-PCR. The miR-22H had extra 13 bases, 5’-TGTGTTCAGTGGT-3’, at the 3’-end, and this segment was named miR-22E. Using ISH, miR-22E overexpression was detected in 225 (83.0%) of 271 LADC patients. A significant difference was found in cumulative survival between patients with high miR-22E levels and those with low miR-22E levels (p < 0.0001). In vitro, epidermal growth factor induced miR-22, but reduced HER-3 expression. Expression of miR-22 increased cell movement ability. In conclusion, expression of miR-22 is closely associated with tumor recurrence, metastasis and overall survival in LADC patients by suppressing HER-3 protein expression to enhance epithelial-mesenchymal transition and metastasis.

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Fang, H. , Lin, T. , Chiou, S. , Wang, L. and Chow, K. (2015) MicroRNA-22E Inhibits HER-3 Protein Expression to Facilitate Metastasis of Lung Adenocarcinomas. Journal of Cancer Therapy, 6, 362-374. doi: 10.4236/jct.2015.64039.

Conflicts of Interest

The authors declare no conflicts of interest.

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