Vilà Maya R, Gelpí Carmen, Nicolás Antoni, Morote Joan, Schwartz Simó, Schwartz Simón, Meseguer Anna
Unit of Molecular Endocrinology, Centre d' Investigacions en Bioquímica i Biologia Molecular (CIBBIM), Hospitals Universitaris Vall d'Hebron, Barcelona, Spain.
Oncol Rep. 2003 Nov-Dec;10(6):1903-9.
Tumor cell growth and differentiation involve several molecular mechanisms that control gene expression and define specific genomic molecular profiles in cancer cells. Among these mechanisms, it has been shown that Alu-repetitive sequences are capable of regulating gene expression at transcriptional and posttranscriptional levels, and also of modulating cellular growth, differentiation and tumor suppression. Furthermore, repetitive sequences have also been implicated in alternative RNA splicing, although the specific mechanisms involved remain unknown. Nonetheless, exactly what the involvement of Alu-containing sequences in tumor cell growth and differentiation is or to what extent they might be related to tumorigenesis or to alternative splicing is not yet clear. In order to address some of these issues, we analyzed the level of expression of Alu-containing sequences in renal tumors and cell lines and their association with immunoprecipitated ribonucleoprotein splicing complexes in nuclear RNA fractions. Over-expression of Alu-containing sequences was detected in the poly(A)-RNA fractions of all analyzed tumors and cell lines. Furthermore, Alu-sequences were associated with tumor cell growth and differentiation and found overexpressed in purified small nuclear ribonucleoprotein fractions. Overall, our results suggest the involvement of Alu-sequences in the overexpression of Alu-containing-mRNAs in human tumors, and also higher processing rates of Alu-containing sequences at the spliceosome associated with tumor cell growth and differentiation.
肿瘤细胞的生长和分化涉及多种分子机制，这些机制控制基因表达并定义癌细胞中的特定基因组分子谱。在这些机制中，已表明Alu重复序列能够在转录和转录后水平调节基因表达，还能调节细胞生长、分化和肿瘤抑制。此外，重复序列也与可变RNA剪接有关，尽管具体机制尚不清楚。然而，含Alu序列在肿瘤细胞生长和分化中的具体作用以及它们与肿瘤发生或可变剪接的相关程度尚不清楚。为了解决其中一些问题，我们分析了肾肿瘤和细胞系中含Alu序列的表达水平及其与核RNA组分中免疫沉淀核糖核蛋白剪接复合物的关联。在所有分析的肿瘤和细胞系的poly(A)-RNA组分中均检测到含Alu序列的过表达。此外，Alu序列与肿瘤细胞生长和分化相关，并在纯化的小核核糖核蛋白组分中过表达。总体而言，我们的结果表明Alu序列参与了人类肿瘤中含Alu mRNA的过表达，并且在与肿瘤细胞生长和分化相关的剪接体处含Alu序列的加工速率更高。
