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 Chow^5*

¹Departments of Surgery, School of Medicine, China Medical University, Taichung.
²Departments of Pathology, China Medical University Hospital, Taichung.
³Graduate Institute of Microbiology and Public Health, Agricultural Biotechnology Center, National Chung Hsing University, Taichung.
⁴Graduate Institution of Clinical Medicine, Medical College, Taipei Medical University, Section of Thoracic Surgery, Departments of Surgery, Taipei Medical University-Shuang Ho Hospital, Taipei city.
⁵Graduate Institute of Biomedical Sciences and Agricultural Biotechnology Center, National Chung Hsing University, Taichung.

DOI: 10.4236/jct.2015.64039                

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.

Keywords

HER-3, Lung Adenocarcinoma, miR-22H, miR-22, EGFR, Epithelial-Mesenchymal Transition, Metastasis

Conflicts of Interest

The authors declare no conflicts of interest.

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