piR-823 contributes to colorectal tumorigenesis by enhancing the transcriptional activity of HSF1.
piR-823 contributes to colorectal tumorigenesis by enhancing the transcriptional activity of HSF1.
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piR-823 通过增强 HSF1 的转录活性促进结直肠肿瘤发生
DOI：
10.1111/cas.13300
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发表时间：
2017-09
期刊：
影响因子：
5.7
通讯作者：
Jiang HQ
中科院分区：
文献类型：
--
作者：
Yin J;Jiang XY;Qi W;Ji CG;Xie XL;Zhang DX;Cui ZJ;Wang CK;Bai Y;Wang J;Jiang HQ
Piwi相互作用RNA（piRNA）是一类新型的小的非编码RNA，首先在生殖细胞中发现，并被认为在精子发生中沉默转座子。最近，也已经在体细胞组织中鉴定出piRNA，并且piRNA在肿瘤组织中的异常表达可能与癌发生有关。然而，piR-823在结直肠癌（CRC）中的功能仍不清楚。在这里，我们首次发现，与其在邻近组织中的表达相比，piR-823在CRC组织中显著上调。在CRC细胞系HCT 116和DLD-1中，抑制piR-823抑制细胞增殖，将细胞周期阻滞在G1期并诱导细胞凋亡，而在正常结肠上皮细胞系FHC中，过表达piR-823促进细胞增殖。有趣的是，piR-823的抑制抑制了热休克蛋白（HSP）的表达27，60，70。此外，升高的HSP表达部分消除了piR-823对细胞增殖和凋亡的影响。此外，我们进一步证明了piR-823通过与HSF 1结合并促进其Ser 326磷酸化来增加HSF 1（HSPs的常见转录因子）的转录活性。我们的研究表明，piR-823通过上调HSF 1的磷酸化和转录活性发挥促肿瘤作用，并表明piR-823是CRC的潜在治疗靶点。
Piwi‐interacting RNAs (piRNAs), a novel class of small non‐coding RNAs, were first discovered in germline cells and are thought to silence transposons in spermatogenesis. Recently, piRNAs have also been identified in somatic tissues, and aberrant expression of piRNAs in tumor tissues may be implicated in carcinogenesis. However, the function of piR‐823 in colorectal cancer (CRC) remains unclear. Here, we first found that piR‐823 was significantly upregulated in CRC tissues compared with its expression in the adjacent tissues. Inhibition of piR‐823 suppressed cell proliferation, arrested the cell cycle in the G1 phase and induced cell apoptosis in CRC cell lines HCT116 and DLD‐1, whereas overexpression of piR‐823 promoted cell proliferation in normal colonic epithelial cell line FHC. Interestingly, Inhibition of piR‐823 repressed the expression of heat shock protein (HSP) 27, 60, 70. Furthermore, elevated HSPs expression partially abolished the effect of piR‐823 on cell proliferation and apoptosis. In addition, we further demonstrated that piR‐823 increased the transcriptional activity of HSF1, the common transcription factor of HSPs, by binding to HSF1 and promoting its phosphorylation at Ser326. Our study reveals that piR‐823 plays a tumor‐promoting role by upregulating phosphorylation and transcriptional activity of HSF1 and suggests piR‐823 as a potential therapeutic target for CRC.
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影响因子：
10.5
作者：
Aravin, Alexei A.;Bourc'his, Deborah
通讯作者：
Bourc'his, Deborah
影响因子：
5.3
作者：
BALER, R;DAHL, G;VOELLMY, R
通讯作者：
VOELLMY, R
影响因子：
3.5
作者：
Lee, JH;Schütte, D;Nayernia, K
通讯作者：
Nayernia, K
DOI：
10.1111/j.1540-8159.1992.tb02971.x
发表时间：
1992-11-01
影响因子：
1.8
作者：
BONGIORNI, MG;SOLDATI, E;BIAGINI, A
通讯作者：
BIAGINI, A
影响因子：
10.5
作者：
Grivna, Shane T.;Beyret, Ergin;Lin, Haifan
通讯作者：
Lin, Haifan