hTERT promotes cell adhesion and migration independent of telomerase activity.
hTERT promotes cell adhesion and migration independent of telomerase activity.
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hTERT 促进细胞粘附和迁移，与端粒酶活性无关
DOI：
10.1038/srep22886
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发表时间：
2016-03-14
影响因子：
4.6
通讯作者：
Zhao Y
中科院分区：
文献类型：
--
作者：
Liu H;Liu Q;Ge Y;Zhao Q;Zheng X;Zhao Y
HTERT是人类端粒酶的催化成分，在正常体细胞中检测不到，但在肿瘤和干细胞中上调，因为端粒长度由端粒酶维持。越来越多的证据表明，hTERT可能通过调节特定基因的表达而具有端粒酶以外的非规范功能。然而，目前尚不能全面鉴定受hTERT调控的基因。在本报告中，我们在人U2OS癌细胞和VA-13永生化成纤维细胞中表达了具有功能失调催化活性的wT hTERT和hTERTmut，这两种细胞都缺乏内源性hTERT和hTERR的表达。用全基因组RNA-seq方法检测hTERT和hTERT-mut基因表达的变化，并用qPCR进行验证。我们的结果表明，hTERT在两个细胞系中影响不同的基因，这意味着hTERT对基因表达的调控是间接的和细胞类型相关的。此外，功能分析确定了两种细胞系中已被hTERT改变的细胞黏附相关基因。黏附实验表明，hTERT的表达显著增加了细胞黏附。单层创面愈合和透气分析显示hTERT表达增加了细胞迁移。这些结果提供了新的证据，支持hTERT在促进肿瘤发生中的非规范功能。
hTERT, a catalytic component of human telomerase, is undetectable in normal somatic cells but up-regulated in cancer and stem cells where telomere length is maintained by telomerase. Accumulated evidence indicates that hTERT may have noncanonical functions beyond telomerase by regulating the expression of particular genes. However, comprehensive identification of the genes regulated by hTERT is unavailable. In this report, we expressed WT hTERT and hTERTmut which displays dysfunctional catalytic activity, in human U2OS cancer cells and VA-13 immortalized fibroblast cells, both of which lack endogenous hTERT and hTR expression. Changes in gene expression induced by hTERT and hTERT-mut expression were determined by genome-wide RNA-seq and verified by qPCR. Our results showed that hTERT affects different genes in two cell lines, implying that the regulation of gene expression by hTERT is indirect and cell type dependent. Moreover, functional analysis identifies cell adhesion-related genes that have been changed by hTERT in both cell lines. Adhesion experiments revealed that hTERT expression significantly increases cell adhesion. Monolayer wound healing and transwell assays demonstrated increased cell migration upon hTERT expression. These results provide new evidence to support a noncanonical function for hTERT in promoting tumorigenesis.