LncRNA-UCA1 enhances cell proliferation and 5-fluorouracil resistance in colorectal cancer by inhibiting miR-204-5p.
LncRNA-UCA1 enhances cell proliferation and 5-fluorouracil resistance in colorectal cancer by inhibiting miR-204-5p.
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DOI：
10.1038/srep23892
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发表时间：
2016-04-05
影响因子：
4.6
通讯作者：
Huang Z
中科院分区：
文献类型：
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作者：
Bian Z;Jin L;Zhang J;Yin Y;Quan C;Hu Y;Feng Y;Liu H;Fei B;Mao Y;Zhou L;Qi X;Huang S;Hua D;Xing C;Huang Z
最近的初步研究报道了长链非编码RNA尿路上皮癌相关1 （UCA1）在结直肠癌（CRC）中的体外肿瘤促进作用。然而，UCA1在结直肠癌中的体内功能和分子机制尚不清楚。因此，我们详细研究了UCA1在CRC中的作用和机制。我们发现，在两个CRC队列中，UCA1在CRC中上调，并与生存时间呈负相关。功能实验揭示了UCA1在体外和体内的促生长功能，发现UCA1可以通过抑制细胞凋亡来降低CRC细胞对5-FU的敏感性。进一步的机制研究表明，UCA1可以海绵内源性miR-204-5p并抑制其活性。我们还发现CREB1是miR-204-5p的新靶点。CRCs中CREB1蛋白水平显著上调，与存活时间呈负相关，与UCA1表达呈正相关。本研究首次提供了CRC中UCA1- mir -204-5p-CREB1/BCL2/RAB22A调控网络的证据，并揭示了UCA1和CREB1是CRC潜在的新癌基因和预后因素。
Recent preliminary studies reported the in vitro tumor-promoting effects of long non-coding RNA urothelial carcinoma associated 1 (UCA1) in colorectal cancer (CRC). However, the in vivo functions and molecular mechanism of UCA1 in CRC remain unclear. Therefore, we investigated the detailed role and mechanism of UCA1 in CRC. We found that UCA1 was up-regulated in CRCs and negatively correlated with survival time in two CRC cohorts. Functional assays revealed the in vitro and in vivo growth-promoting function of UCA1 and revealed that UCA1 can decrease the sensitivity of CRC cells to 5-FU by attenuating apoptosis. Further mechanistic studies revealed that UCA1 could sponge endogenous miR-204-5p and inhibit its activity. We also identified CREB1 as a new target of miR-204-5p. The protein levels of CREB1 were significantly up-regulated in CRCs, negatively associated with survival time and positively correlated with the UCA1 expression. The present work provides the first evidence of a UCA1-miR-204-5p-CREB1/BCL2/RAB22A regulatory network in CRC and reveals that UCA1 and CREB1 are potential new oncogenes and prognostic factors for CRC.