Long noncoding RNA small nucleolar RNA host gene 4 (SNHG4) is usually up-regulated in cancer and regulates the malignant behavior of cancer cells. However, its role in lung cancer remains elusive. In this study, we silenced the expression of SNHG4 in NCI-H1437 and SK-MES-1, two representative non-small-cell lung cancer cell lines, by transfecting them with siRNA (small interfering RNA) that specifically targets SNHG4. We observed significantly inhibited cell proliferation in vitro and reduced tumor growth in vivo after SNHG4 silencing. SNHG4 knockdown also led to cell cycle arrest at the G1 phase, accompanied with down-regulation of cyclin-dependent kinases CDK4 and CDK6. The migration and invasiveness of these two cell lines were remarkably inhibited after SNHG4 silencing. Moreover, our study revealed that the epithelial-mesenchymal transition (EMT) of lung cancer cells was suppressed by SNHG4 silencing, as evidenced by up-regulated E-cadherin and down-regulated SALL4, Twist, and vimentin. In addition, we found that SNHG4 silencing induced up-regulation of miR-98-5p. MiR-98-5p inhibition abrogated the effect of SNHG4 silencing on proliferation and invasion of lung cancer cells. In conclusion, our findings demonstrate that SNHG4 is required by lung cancer cells to maintain malignant phenotype. SNHG4 probably exerts its pro-survival and pro-metastatic effects by sponging anti-tumor miR-98-5p.

中文翻译：

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LncRNA SNHG4通过调节miR-98-5p促进肺癌细胞的增殖，迁移，侵袭性和上皮-间质转化。

长非编码RNA小核仁RNA宿主基因4（SNHG4）通常在癌症中上调，并调节癌细胞的恶性行为。但是，其在肺癌中的作用仍然难以捉摸。在这项研究中，我们通过用特异性靶向SNHG4的siRNA（小干扰RNA）转染NCI-H1437和SK-MES-1（两种代表性的非小细胞肺癌细胞系）来沉默SNHG4的表达。我们观察到SNHG4沉默后在体外显着抑制细胞增殖，并在体内降低肿瘤生长。SNHG4敲低还导致细胞周期停滞在G1期，伴随着细胞周期蛋白依赖性激酶CDK4和CDK6的下调。SNHG4沉默后，这两个细胞系的迁移和侵袭性受到明显抑制。此外，我们的研究表明，SNHG4沉默可抑制肺癌细胞的上皮-间质转化（EMT），如上调E-钙粘蛋白和下调SALL4，Twist和波形蛋白所证明的。此外，我们发现SNHG4沉默诱导miR-98-5p的上调。MiR-98-5p抑制消除了SNHG4沉默对肺癌细胞增殖和侵袭的影响。总之，我们的发现表明，肺癌细胞需要SNHG4才能维持恶性表型。SNHG4可能通过抵抗抗肿瘤miR-98-5p发挥其促生存和促转移作用。MiR-98-5p抑制消除了SNHG4沉默对肺癌细胞增殖和侵袭的影响。总之，我们的发现表明，肺癌细胞需要SNHG4才能维持恶性表型。SNHG4可能通过抵抗抗肿瘤miR-98-5p发挥其促生存和促转移作用。MiR-98-5p抑制消除了SNHG4沉默对肺癌细胞增殖和侵袭的影响。总之，我们的发现表明，肺癌细胞需要SNHG4才能维持恶性表型。SNHG4可能通过抵抗抗肿瘤miR-98-5p发挥其促生存和促转移作用。