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10780432ccr112857-sup-fig3.pdf (154.05 kB)

Supplementary Figure 3 from Increased miR-708 Expression in NSCLC and Its Association with Poor Survival in Lung Adenocarcinoma from Never Smokers

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posted on 2023-03-31, 17:05 authored by Jin Sung Jang, Hyo-Sung Jeon, Zhifu Sun, Marie Christine Aubry, Hui Tang, Cheol-Hong Park, Fariborz Rakhshan, Debra A. Schultz, Christopher P. Kolbert, Ruth Lupu, Jae Yong Park, Curtis C. Harris, Ping Yang, Jin Jen

PDF file, 154KB, TMEM88 is a putative target of miR-708 by MicroCosm database. The target site of miR-708 is located in the 3'UTR, 286 to 309 bases from downstream of the stop codon sequence of TMEM88. Asterisks indicate the binding site.

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ARTICLE ABSTRACT

Purpose: miRNA plays an important role in human disease and cancer. We seek to investigate the expression status, clinical relevance, and functional role of miRNA in non–small cell lung cancer.Experimental Design: We conducted miRNA expression profiling in matched lung adenocarcinoma and uninvolved lung using 56 pairs of fresh-frozen (FF) and 47 pairs of formalin-fixed, paraffin-embedded (FFPE) samples from never smokers. The most differentially expressed miRNA genes were evaluated by Cox analysis and log-rank test. Among the best candidate, miR-708 was further examined for differential expression in two independent cohorts. Functional significance of miR-708 expression in lung cancer was examined by identifying its candidate mRNA target and through manipulating its expression levels in cultured cells.Results: Among the 20 miRNAs most differentially expressed between tested tumor and normal samples, high expression level of miR-708 in the tumors was most strongly associated with an increased risk of death after adjustments for all clinically significant factors including age, sex, and tumor stage (FF cohort: HR, 1.90; 95% CI, 1.08–3.35; P = 0.025 and FFPE cohort: HR, 1.93; 95% CI, 1.02–3.63; P = 0.042). The transcript for TMEM88 gene has a miR-708 binding site in its 3′ UTR and was significantly reduced in tumors high of miR-708. Forced miR-708 expression reduced TMEM88 transcript levels and increased the rate of cell proliferation, invasion, and migration in culture.Conclusions: miRNA-708 acts as an oncogene contributing to tumor growth and disease progression by directly downregulating TMEM88, a negative regulator of the Wnt signaling pathway in lung cancer. Clin Cancer Res; 18(13); 3658–67. ©2012 AACR.

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