a Department of Radiation Oncology , Peking Union Medical College Hospital , Beijing , China.
b State Key Laboratory of Molecular Oncology , Peking Union medical College Hospital Cancer Hospital, Chinese Academy of Medical Sciences , Beijing , China.
Cancer Biol Ther. 2018;19(12):1185-1192. doi: 10.1080/15384047.2018.1491505. Epub 2018 Sep 19.
Small cell lung cancer (SCLC) is a highly aggressive disease and miRNAs may play an important role in modulating SCLC progression. We have previously screened 924 miRNAs and found that miR-886-3P was negatively associated with SCLC survival. In the current study, we further investigated the role of miR-886-3P mimic in regulating SCLC cell phenotypic alteration in vitro and xenograft tumor formation in vivo. We found that transfection of miR-886-3P mimic significantly inhibited SCLC cell proliferation, migration, and colony formation, and induced mesenchymal-epithelial transition (MET) by suppressing TGF-ß1 synthesis in vitro. Furthermore, intra-tumor injection of miR-886-3P mimic lead to necrosis and suppression of tumor invasion to the surrounding tissue in the subcutaneous xenograft tumor, and intra-vein injection of miR-886-3P mimic suppressed xenograft lung cancer growth in vivo. These findings suggested that miR-886-3P functions as a tumor suppressor in SCLC and thus, it might be a potential therapeutic molecule in the treatment of lung cancer.
小细胞肺癌(SCLC)是一种高度侵袭性疾病,miRNAs 可能在调节 SCLC 进展中发挥重要作用。我们之前筛选了 924 个 miRNAs,发现 miR-886-3P 与 SCLC 患者的生存呈负相关。在本研究中,我们进一步研究了 miR-886-3P 模拟物在体外调节 SCLC 细胞表型改变和体内异种移植肿瘤形成中的作用。我们发现,miR-886-3P 模拟物的转染显著抑制了 SCLC 细胞的增殖、迁移和集落形成,并通过抑制 TGF-β1 的合成在体外诱导间充质-上皮转化(MET)。此外,肿瘤内注射 miR-886-3P 模拟物导致皮下异种移植瘤中的肿瘤坏死和抑制肿瘤向周围组织侵袭,静脉内注射 miR-886-3P 模拟物抑制了体内异种移植肺癌的生长。这些发现表明,miR-886-3P 在 SCLC 中作为肿瘤抑制因子发挥作用,因此,它可能是治疗肺癌的潜在治疗分子。