Abstract
The non-small-cell lung cancer (NSCLC) is the most common type of lung cancer that affects the human health. But, the underlying mechanisms and effective therapy are still absent. MicroRNAs (miRNAs) are small RNAs that specifically bind to the 3′ untranslated region (3′UTR) of its target and regulate the protein level of the target at post-transcriptional level. A lot of miRNAs had been found abnormally regulated in the NSCLC patients, and understanding their specific roles in the pathogenesis of NSCLC will help us to develop novel therapeutic approaches. Here, we reported that miR-25 is dramatically upregulated in NSCLC tissues and negatively correlated with RGS3 protein. A conserved binding sequence in the 3′UTR of RGS3 gene to miR-25 was identified, and overexpression of miR-25 induces the RGS3 inhibition. Importantly, suppression of miR-25 facilitates the cell apoptosis and retards the cell proliferation in A549 and H520 cell lines. Our data provide a novel miR-25/RGS3 signal in the development of lung cancer.
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References
Chen K, Rajewsky N (2007) The evolution of gene regulation by transcription factors and microRNAs. Nat Rev Genet 8:93–103
Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X et al (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18:997–1006
Dulin NO, Pratt P, Tiruppathi C, Niu J, Voyno-Yasenetskaya T, Dunn MJ (2000) Regulator of G protein signaling RGS3T is localized to the nucleus and induces apoptosis. J Biol Chem 275:21317–21323
Dulin NO, Sorokin A, Reed E, Elliott S, Kehrl JH, Dunn MJ (1999) RGS3 inhibits G protein-mediated signaling via translocation to the membrane and binding to Galpha11. Mol Cell Biol 19:714–723
Granville CA, Dennis PA (2005) An overview of lung cancer genomics and proteomics. Am J Respir Cell Mol Biol 32:169–176
Han SW, Roman J (2010) Targeting apoptotic signaling pathways in human lung cancer. Curr Cancer Drug Targets 10:566–574
He Z, Liu Y, **ao B, Qian X (2015) miR-25 modulates NSCLC cell radio-sensitivity through directly inhibiting BTG2 expression. Biochem Biophys Res Commun 457:235–241
Lin PY, Yu SL, Yang PC (2010) MicroRNA in lung cancer. Br J Cancer 103:1144–1148
Murchison EP, Hannon GJ (2004) miRNAs on the move: miRNA biogenesis and the RNAi machinery. Curr Opin Cell Biol 16:223–229
Nakamura H, Taniguchi Y, Miwa K, Adachi Y, Fujioka S, Haruki T, Takagi Y, Yurugi Y (2011) Comparison of the surgical outcomes of thoracoscopic lobectomy, segmentectomy, and wedge resection for clinical stage I non-small cell lung cancer. Thorac Cardiovasc Surg 59:137–141
Nishiura H, Nonaka H, Revollo IS, Semba U, Li Y, Ota Y, Irie A, Harada K, Kehrl JH, Yamamoto T (2009) Pro- and anti-apoptotic dual functions of the C5a receptor: involvement of regulator of G protein signaling 3 and extracellular signal-regulated kinase. Lab Investig J Tech Methods Pathol 89:676–694
Sankpal UT, Pius H, Khan M, Shukoor MI, Maliakal P, Lee CM, Abdelrahim M, Connelly SF, Basha R (2012) Environmental factors in causing human cancers: emphasis on tumorigenesis. Tumour Biol J Int Soc Oncodev Biol Med 33:1265–1274
Sethakorn N, Dulin NO (2013) RGS expression in cancer: oncomining the cancer microarray data. J Recept Signal Transduct Res 33:166–171
Siegel R, Ward E, Brawley O, Jemal A (2011) Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA: Cancer J Clin 61:212–236
Tatenhorst L, Senner V, Puttmann S, Paulus W (2004) Regulators of G-protein signaling 3 and 4 (RGS3, RGS4) are associated with glioma cell motility. J Neuropathol Exp Neurol 63:210–222
Workman ML, Winkelman C (2008) Genetic influences in common respiratory disorders. Crit Care Nur Clin North Am 20:171–189, vi
Xu FX, Su YL, Zhang H, Kong JY, Yu H, Qian BY (2014) Prognostic implications for high expression of MiR-25 in lung adenocarcinomas of female non-smokers. Asian Pac J Cancer Prev: APJCP 15:1197–1203
Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T et al (2006) Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 9:189–198
Yang T, Chen T, Li Y, Gao L, Zhang S, Wang T, Chen M (2015) Downregulation of miR-25 modulates non-small cell lung cancer cells by targeting CDC42. Tumour Biol J Int Soc Oncodev Biol Med 36:1903–1911
Zhang N, Su Y, Xu L (2013) Targeting PKCepsilon by miR-143 regulates cell apoptosis in lung cancer. FEBS Lett 587:3661–3667
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Editor: Tetsuji Okamoto
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Chen, Z., Wu, Y., Meng, Q. et al. Elevated microRNA-25 inhibits cell apoptosis in lung cancer by targeting RGS3. In Vitro Cell.Dev.Biol.-Animal 52, 62–67 (2016). https://doi.org/10.1007/s11626-015-9947-2
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DOI: https://doi.org/10.1007/s11626-015-9947-2