Lin Heping, Shangguan Zongxiao, Zhu Mengchu, Bao Lianmin, Zhang Qing, Pan Shenghua
Department of Respiratory Diseases, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Clinical Laboratory, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
J Cell Biochem. 2019 Jun;120(6):10625-10632. doi: 10.1002/jcb.28352. Epub 2019 Jan 29.
Long noncoding RNAs have been reported to be essential regulators in several human diseases, including tumorigenesis. A recent report revealed that FLVCR1-AS1 promotes the progression of hepatocellular carcinoma. However, whether FLVCR1-AS1 is involved in lung cancer remains unclear. In this study, we found that the expression of FLVCR1-AS1 was increased in lung cancer tissues according to The Cancer Genome Atlas database. Similarly, FLVCR1-AS1 was significantly upregulated in lung cancer cell lines. Knockdown of FLVCR1-AS1 dramatically reduced the cell proliferation, migration, and invasion of SPCA1 and A549. Mechanistically, we found that the expression levels of CTNNB1, SOX4, CCND1, CCND2, c-MYC, as well as nucleus β-catenin were decreased in lung cancer cells after FLVCR1-AS1 silencing. Thus, FLVCR1-AS1 positively regulates the activation of the Wnt/β-catenin pathway. Overexpression of CTNNB1 reversed the effect of FLVCR1-AS1 knockdown on A549 cells. In sum, FLVCR1-AS1 silencing inhibited the proliferation, migration, and invasion of lung cancer cells by inhibiting the activity of the Wnt/β-catenin signaling pathway.
据报道，长链非编码RNA是包括肿瘤发生在内的多种人类疾病的重要调节因子。最近的一份报告显示，FLVCR1-AS1促进肝细胞癌的进展。然而，FLVCR1-AS1是否参与肺癌仍不清楚。在本研究中，根据癌症基因组图谱数据库，我们发现FLVCR1-AS1在肺癌组织中的表达增加。同样，FLVCR1-AS1在肺癌细胞系中显著上调。敲低FLVCR1-AS1可显著降低SPCA1和A549细胞的增殖、迁移和侵袭能力。机制上，我们发现FLVCR1-AS1沉默后，肺癌细胞中CTNNB1、SOX4、CCND1、CCND2、c-MYC以及细胞核β-连环蛋白的表达水平降低。因此，FLVCR1-AS1正向调节Wnt/β-连环蛋白通路的激活。CTNNB1的过表达逆转了FLVCR1-AS1敲低对A549细胞的影响。总之，FLVCR1-AS1沉默通过抑制Wnt/β-连环蛋白信号通路的活性，抑制肺癌细胞的增殖、迁移和侵袭。
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