Primate-specific oestrogen-responsive long non-coding RNAs regulate proliferation and viability of human breast cancer cells.
Primate-specific oestrogen-responsive long non-coding RNAs regulate proliferation and viability of human breast cancer cells.
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DOI：
10.1098/rsob.150262
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发表时间：
2016-12
期刊：
影响因子：
5.8
通讯作者：
Lipovich L
中科院分区：
文献类型：
--
作者：
Lin CY;Kleinbrink EL;Dachet F;Cai J;Ju D;Goldstone A;Wood EJ;Liu K;Jia H;Goustin AS;Kosir MA;Thepsuwan P;Lipovich L
长链非编码RNA（lncRNA）是最近发现的一类不编码蛋白质的基因的转录物。在人类基因组中，LncRNA基因的数量与蛋白质编码基因的数量大致相同。然而，对于lncRNA的功能知之甚少。我们全面询问了雌激素受体阳性的人乳腺癌细胞在雌激素治疗后lncRNA转录组的变化，并确定了127个雌激素反应性lncRNA。与大多数人类lncRNA基因缺乏灵长类动物以外的同源物的新证据相一致，我们的进化分析揭示了雌激素信号下游的灵长类动物特异性lncRNA。我们证明，使用多种功能检测来探测两种雌激素受体阳性人乳腺癌细胞系的功能获得和丧失表型，本研究中鉴定的两种灵长类特异性雌激素应答lncRNA，（雌激素抑制的lncRNA BC 041455，其降低细胞活力，和雌激素诱导的lncRNA CR 593775，其增加细胞活力）在细胞增殖和生长因子信号传导途径中发挥以前未被认识的功能。结果表明，雌激素反应性lncRNA能够改变人乳腺癌细胞的增殖和活力。对细胞表型的影响与对照转染无关。作为迄今为止未被认识到的癌症中的关键信号传导途径（包括MAP激酶途径）的组分，lncRNA因此代表雌激素对细胞增殖和活力表型的作用的新机制。这一发现保证了在乳腺癌和潜在的其他类型的癌症的基础和翻译研究中的进一步调查，与其他核激素受体途径中的lncRNA具有广泛的相关性，并且应该有助于在后基因组治疗中利用和靶向这些细胞活力调节lncRNA。
Long non-coding RNAs (lncRNAs) are transcripts of a recently discovered class of genes which do not code for proteins. LncRNA genes are approximately as numerous as protein-coding genes in the human genome. However, comparatively little remains known about lncRNA functions. We globally interrogated changes in the lncRNA transcriptome of oestrogen receptor positive human breast cancer cells following treatment with oestrogen, and identified 127 oestrogen-responsive lncRNAs. Consistent with the emerging evidence that most human lncRNA genes lack homologues outside of primates, our evolutionary analysis revealed primate-specific lncRNAs downstream of oestrogen signalling. We demonstrate, using multiple functional assays to probe gain- and loss-of-function phenotypes in two oestrogen receptor positive human breast cancer cell lines, that two primate-specific oestrogen-responsive lncRNAs identified in this study (the oestrogen-repressed lncRNA BC041455, which reduces cell viability, and the oestrogen-induced lncRNA CR593775, which increases cell viability) exert previously unrecognized functions in cell proliferation and growth factor signalling pathways. The results suggest that oestrogen-responsive lncRNAs are capable of altering the proliferation and viability of human breast cancer cells. No effects on cellular phenotypes were associated with control transfections. As heretofore unappreciated components of key signalling pathways in cancers, including the MAP kinase pathway, lncRNAs hence represent a novel mechanism of action for oestrogen effects on cellular proliferation and viability phenotypes. This finding warrants further investigation in basic and translational studies of breast and potentially other types of cancers, has broad relevance to lncRNAs in other nuclear hormone receptor pathways, and should facilitate exploiting and targeting these cell viability modulating lncRNAs in post-genomic therapeutics.
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DOI：
10.1038/mtna.2014.45
发表时间：
2014-11-18
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.7
作者：
Abreu MM;Sealy L
通讯作者：
Sealy L
DOI：
10.1093/jnci/53.3.661
发表时间：
1974-01-01
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
CAILLEAU, R;YOUNG, R;REEVES, WJ
通讯作者：
REEVES, WJ
影响因子：
12.3
作者：
Lin CY;Ström A;Vega VB;Kong SL;Yeo AL;Thomsen JS;Chan WC;Doray B;Bangarusamy DK;Ramasamy A;Vergara LA;Tang S;Chong A;Bajic VB;Miller LD;Gustafsson JA;Liu ET
通讯作者：
Liu ET
影响因子：
4.5
作者：
Lin CY;Vega VB;Thomsen JS;Zhang T;Kong SL;Xie M;Chiu KP;Lipovich L;Barnett DH;Stossi F;Yeo A;George J;Kuznetsov VA;Lee YK;Charn TH;Palanisamy N;Miller LD;Cheung E;Katzenellenbogen BS;Ruan Y;Bourque G;Wei CL;Liu ET
通讯作者：
Liu ET