Division of Systems Medicine & Gene Therapy, Saitama Medical University, Hidaka, Saitama 350-1241, Japan.
Department of Systems Aging Science and Medicine, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173-0015, Japan.
Int J Mol Sci. 2021 Oct 18;22(20):11242. doi: 10.3390/ijms222011242.
Patients with advanced ovarian cancer usually exhibit high mortality rates, thus more efficient therapeutic strategies are expected to be developed. Recent transcriptomic studies revealed that long intergenic noncoding RNAs (lincRNAs) can be a new class of molecular targets for cancer management, because lincRNAs likely exert tissue-specific activities compared with protein-coding genes or other noncoding RNAs. We here show that an unannotated lincRNA originated from chromosome 10q21 and designated as (), is often overexpressed in ovarian cancer tissues compared with normal ovaries as analyzed by RNA sequencing. silencing by specific siRNAs significantly exerted proliferation inhibition and enhanced apoptosis in ovarian cancer cells. Notably, RNA sequencing showed that expression was negatively correlated with the expression of apoptosis-related genes () and (), which were upregulated by knockdown in ovarian cancer cells. -specifc siRNA injection was effective to suppress in vivo tumor growth of ovarian cancer cells inoculated in immunodeficient mice. Taken together, could function as a tumor-promoting lincRNA in ovarian cancer through modulating apoptosis and will be a potential molecular target for ovarian cancer management.
患有晚期卵巢癌的患者通常表现出高死亡率，因此需要开发更有效的治疗策略。最近的转录组学研究表明，长链非编码 RNA（lncRNA）可能成为癌症管理的一类新的分子靶点，因为 lincRNA 可能与蛋白质编码基因或其他非编码 RNA 相比具有组织特异性活性。我们在这里表明，来自 10q21 染色体并被指定为 （）的未注释 lincRNA，在 RNA 测序分析中与正常卵巢相比，在卵巢癌组织中常常过度表达。通过特异性 siRNA 沉默显着抑制卵巢癌细胞的增殖并增强凋亡。值得注意的是，RNA 测序显示， 表达与凋亡相关基因 （）和 （）的表达呈负相关，而这两种基因在卵巢癌细胞中被 下调后被上调。在免疫缺陷小鼠中接种卵巢癌细胞的体内肿瘤生长中， 特异性 siRNA 注射有效抑制了肿瘤生长。总之， 可通过调节凋亡在卵巢癌中作为促肿瘤 lincRNA 发挥作用，并且可能成为卵巢癌管理的潜在分子靶标。
