Tuberc Respir Dis.  2009 Nov;67(5):413-421.

MicroRNA Expression Profiles in Korean Non-Small Cell Lung Cancer

Affiliations
  • 1Department of Internal Medicine, Konyang University Hospital, Daejeon, Korea.
  • 2Department of Thoracic Surgery, Konyang University Hospital, Daejeon, Korea.
  • 3Myunggok Research Institute for Medical Science, Konyang University, Daejeon, Korea.
  • 4Department of Biochemistry, Kyungpook National University School of Medicine, Daegu, Korea. jaeyong@knu.ac.kr
  • 5Department of Hospital Pathology, Daejeon St. Mary's Hospital, Daejeon, Korea.
  • 6Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea.

Abstract

BACKGROUND
MicroRNAs (miRNAs) play an important role in the regulation of cell proliferation, apoptosis, development and differentiation. Several studies have shown that aberrant expression of miRNAs is involved in cancer development and progression by regulating the expression of proto-oncogenes or tumor suppressor genes. In this study, we investigated miRNA expression profiles in Korean patients with non-small cell lung cancer (NSCLC).
METHODS
We performed miRNA microarray analysis containing 60~65 bp oligonucleotide probes representing human 318 miRNAs and validated the results of the microarray with Northern blot analysis or quantitative RT-PCR. Next, we examined the correlation between miRNA expression and the target gene transcriptional profile using a human whole-genome-expression microarray.
RESULTS
We showed that 35 miRNAs were expressed differentially in the NSCLCs and corresponding non-malignant lung tissues. We showed that 35 miRNAs were expressed differentially in the NSCLCs and corresponding non-malignant lung tissues. Thirteen of the 35 differentially expressed miRNAs were newly identified in the present study. Of the 35 miRNAs, 2 (miR-371 and miR-210) were over-expressed in lung cancers, and 33 miRNAs, including miR-145, were under-expressed in lung cancers. miR-99b expression consistently showed a negative correlation with FGFR3 expression.
CONCLUSION
Albeit a small number of patients were examined, these results suggest that miRNA expression profiles in Korean lung cancers may be somewhat different from the expression profiles reported on lung cancers in Western populations. The findings suggest that miR-99b might be a tumor suppressor through its up-regulation of FGFR3.

Keyword

MicroRNAs; Carcinoma, Non-Small-Cell Lung; Korea

MeSH Terms

Apoptosis
Blotting, Northern
Carcinoma, Non-Small-Cell Lung
Cell Proliferation
Genes, Tumor Suppressor
Humans
Korea
Lung
Lung Neoplasms
Microarray Analysis
MicroRNAs
Oligonucleotide Probes
Proto-Oncogenes
Up-Regulation
MicroRNAs
Oligonucleotide Probes

Figure

  • Figure 1 Unsupervised hierarchical clustering of 315 miRNA expression patterns in non-small cell carcinomas and corresponding non-malignant lung tissues. Ratios of miRNA expression are displayed colorimeterically in lung cancers relative to non-malignant lung tissues. The scale bar at the right side represents the relative level of expression of each miRNA. Columns represent array and miRNAs are represented in rows.

  • Figure 2 (A) Northern blot analysis for has-miR-145 and has-miR-210 in four paired lung cancers and corresponding non-malignant lung tissues. Has-miR-210 was up-regulated in lung cancers, and has-miR-145 was down-regulated in lung cancers. (B) Quantitative RT-PCR (qRT-PCR) of miRNA expression utilized total RNA isolated from cancer tissues and non-malignant lung tissues. The expression of miRNA was normalized to 18S rRNA expression and was performed in duplicate. Has-miR-29c was down-regulated in lung cancers (p=0.0001, Mann-Whitney's U test), whereas has-miR-210 was up-regulated in lung cancer (p=0.1295), although statistically not significant.


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