College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China.
Department of Neurology, The First Hospital of Jilin University, Changchun, 130021, China.
Biochem Biophys Res Commun. 2018 Sep 26;504(1):34-39. doi: 10.1016/j.bbrc.2018.08.115. Epub 2018 Sep 1.
Long noncoding RNAs (lncRNAs) are acknowledged as crucial regulators involved in multiple pathological processes, including cancer. Although some lncRNAs are studied in melanoma, the association between lncRNA and melanoma progression still remains vague. And the function of LINC00963 in melanoma is waiting for investigation. In this study, upregulated level of LINC00963 in melanoma tissues was observed. Notably, we found DNA copy-number-gain of LINC00963 contributes to its high expression. And high expression of LINC00963 predicts poor prognosis in patients with melanoma. Functional investigation indicated that LINC00963 knockdown dramatically suppressed melanoma cell proliferation, migration and invasion. Mechanistically, we found that LINC00963 could interact with miR-608 while miR-608 could target NACC1. Upregulated LINC00963 led to elevated expression of NACC1 through inhibiting miR-608, which consequently promoted melanoma malignant progression. Taken together, our results illustrated that LINC00963-miR-608-NACC1 pathway might be a potential target for melanoma therapy.
长链非编码 RNA（lncRNA）被认为是参与多种病理过程（包括癌症）的重要调控因子。尽管一些 lncRNA 在黑色素瘤中得到了研究，但 lncRNA 与黑色素瘤进展之间的关系仍然不清楚。LINC00963 在黑色素瘤中的功能仍有待研究。在本研究中，观察到黑色素瘤组织中 LINC00963 的表达上调。值得注意的是，我们发现 LINC00963 的 DNA 拷贝数增加导致其高表达。LINC00963 的高表达预示着黑色素瘤患者预后不良。功能研究表明，LINC00963 的敲低显著抑制了黑色素瘤细胞的增殖、迁移和侵袭。机制上，我们发现 LINC00963 可以与 miR-608 相互作用，而 miR-608 可以靶向 NACC1。上调的 LINC00963 通过抑制 miR-608 导致 NACC1 的表达升高，从而促进黑色素瘤的恶性进展。总之，我们的研究结果表明，LINC00963-miR-608-NACC1 通路可能是黑色素瘤治疗的潜在靶点。
