中文摘要
长链非编码RNA在肿瘤中的功能和机制复杂多样,与多种肿瘤恶性增殖、转移相关。我们发现并命名了一胃癌来源的长链非编码RNA—KRT7-AS。它的高表达会促进胃癌细胞增殖以及淋巴结转移。它转录自DNA反义链,功能具有“位置特异性”,可通过核酸互补序列与正义链“伙伴”KRT7 mRNA形成RNA-RNA复合体,增加mRNA稳定性,间接增加KRT7蛋白表达。本研究中我们进一步推测KRT7-AS还具有转运功能,可以将KRT7 mRNA从核内转运到胞浆,并通过非互补序列(更确切的说是SINE重复)激活核糖体,增加KRT7蛋白翻译,使得少量的反义长链非编码RNA发挥充分作用。因此本研究旨在深入研究胃癌中KRT7-AS上调KRT7蛋白表达的分子机制,丰富反义长链非编码RNA的理论知识;并探讨它与胃癌增殖、转移以及预后等临床特点的关系,以期探索KRT7-AS作为早期识别胃癌恶性增殖转移分子标志物的可能性。
英文摘要
The role and mechanism of long non-coding RNA (lncRNA) in cancers is complicated and versatile. It involves in malignant proliferation and metastasis in several kinds of tumors. Recently, our group has studied lncRNAs in this context. We identified and named one long non-coding RNA (lncRNA) in gastric cancer (GC). In particular, KRT7-AS, which was greatly overexpressed in GC-derived cell lines and tissue specimens, and was significantly correlated with tumor size and lymph node metastasis in GC. KRT7-AS is also an antisense long non-coding RNA (AS lncRNA), which could exert function through its sense mRNA partner in a locus-specific manner. We found KRT7-AS upregulated its sense cognate partner gene, KRT7, by stabilizing its mRNA, leading to reduced mRNA degradation and increased KRT7 protein levels as well as promoting proliferation and metastasis in GC cells. Based on these previous findings, we now hypothesize that lncRNA KRT7-AS specifically targets KRT7 mRNA at its complementary sequence (i.e., its KRT7 mRNA-overlapping region), then “shuttles” KRT7 mRNA from the nucleus to the cytoplasmic polysome. Moreover, we also now posit that the non-complementary sequence of KRT7-AS (i.e., its non-KRT7 mRNA-overlapping region), more specifically SINE repeat within this sequence, activates the polysome to increase KRT7 protein translation. In summary, we now propose to elucidate the regulatory mechanism underlying KRT7-AS’s stimulation of KRT7 protein expression, which may rich the theory of AS lncRNA; to characterize the clinical significance of its promotion of cell proliferation and migration in GC, which may ultimately reveal the potential of KRT7-AS as a novel marker to early identify malignant proliferation and metastasis in GC.
