Liu Chao, Ji Le, Song Xue
Department of Gastroenterology, Affiliated Hospital of Yan'an University No. 43 North Street Yan'an 716000 Shaanxi China
RSC Adv. 2019 May 7;9(25):14160-14166. doi: 10.1039/c8ra10468a.
The estimated number of new cases of colorectal cancer (CRC) will increase to 140 250 in 2018 worldwide. The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has recently been shown to be dysregulated in CRC, which plays an important role in the progression of CRC. However, the biological role and the underling mechanism of UCA1 in the carcinogenesis of CRC remain unclear. Herein, we found that UCA1 was aberrantly upregulated in two CRC cell lines (SW620 and HT29) compared to colorectal cell CCD-18Co. UCA1 knockdown inhibited the apoptosis, growth and autophagy of CRC cell lines . Furthermore, UCA1 could act as an endogenous sponge by directly interacting with miR-185-5p and downregulation miR-185-5p expression. In addition, UCA1 could reverse the inhibitory effect of miR-185-5p on the growth and autophagy of CRC cells, which might be involved in the derepression of member 1 (WNT1)-inducible signaling pathway protein 2 (WISP2, a target gene of miR-185-5p) expression and the activation of the WISP2/β-catenin signaling pathway. , the present study elucidates a novel UCA1-miR-185-5p-WISP2-Wnt/β-catenin axis in CRC, which may help us to understand the pathogenesis and the feasibility of lncRNA-directed diagnosis and therapy of CRC.
据估计，2018年全球结直肠癌（CRC）新发病例数将增至140250例。长链非编码RNA（lncRNA）尿路上皮癌相关1（UCA1）最近被证明在CRC中表达失调，在CRC进展中起重要作用。然而，UCA1在CRC致癌作用中的生物学作用及潜在机制仍不清楚。在此，我们发现与结肠直肠细胞CCD-18Co相比，UCA1在两种CRC细胞系（SW620和HT29）中异常上调。敲低UCA1可抑制CRC细胞系的凋亡、生长和自噬。此外，UCA1可通过直接与miR-185-5p相互作用并下调miR-185-5p表达，充当内源性海绵。另外，UCA1可逆转miR-185-5p对CRC细胞生长和自噬的抑制作用，这可能与解除对1号成员（WNT1）诱导信号通路蛋白2（WISP2，miR-185-5p的靶基因）表达的抑制及WISP2/β-连环蛋白信号通路的激活有关。本研究阐明了CRC中一条新的UCA1-miR-185-5p-WISP2-Wnt/β-连环蛋白轴，这可能有助于我们了解CRC的发病机制以及lncRNA导向的CRC诊断和治疗的可行性。
