Long non coding RNA UCA1 contributes to the autophagy and survival of colorectal cancer cellsviasponging miR-185-5p to up-regulate the WISP2/β-catenin pathway

Abstract

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 in vitro. 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/b-catenin signaling pathway. In vivo, the present study elucidates a novel UCA1-miR-185-5p-WISP2-Wnt/b-catenin axis in CRC, which may help us to understand the pathogenesis and the feasibility of lncRNA-directed diagnosis and therapy of CRC. Materials and methods Cell cultureNormal colorectal cell CCD-18Co, normal epithelial cell HIEC-6, CRC-derived cells SW620 and HT29 were purchased from ATCC (Manassas, VA, USA). Cells were cultured in RPMI1640 (HyClone, UT, USA) or DMEM (HyClone) which was supplemented with 10% FBS (Gibco, NY, USA), 100 U ml À1 penicillin/streptomycin (HyClone) at 37 C in a humidied incubator with 5% CO 2 . Reagents and transfectionsThe miR-185 inhibitor, sh-UCA1, and sh-UCA1 control sequences were purchased from the GenePharma Company

Long Noncoding RNA (lncRNA)-Mediated Competing Endogenous RNA Networks Provide Novel Potential Biomarkers and Therapeutic Targets for Colorectal Cancer

“…Knockdown of HAGLROS efficiently inhibited autophagy and induced apoptosis via the ceRNA network linking autophagy-related miRNA and proteins. In addition, Liu et al reported that lncRNA UCA1 contributed to the autophagy of CRC cells by harboring miR-185-5p to activate the WNT1-inducible signaling pathway protein 2 (WISP2)/β-catenin pathway [99].…”

Non-coding RNA and autophagy: Finding novel ways to improve the diagnostic management of bladder cancer

“…The overexpression of UCA1 was shown to abrogate apoptotic cell death and facilitate acquired resistance during anti-cancer therapy in bladder cancer cells ( Wang et al, 2017 ). This study has demonstrated that increased overexpression of UCA1 decreased the sensitivity of tamoxifen and silencing of UCA1 mediates/enhances drug sensitivity by induction of apoptosis and cell cycle arrest during tamoxifen treatment ( Liu et al, 2019 ). Mechanistically, UCA1 was shown to physically interact with EZH2, which blocked the p21 expression through histone methylation, and parallelly UCA1 expression mediates phosphorylation of CAMP responsive element binding protein (CREB) and PI3K/AKT and thereby facilitates tamoxifen-mediated resistance ( Fan et al, 2014b ).…”

“…The role of UCA1 in colorectal cancer cells (CRC) has also been studied. A study by Liu et al demonstrated that the UCA1-Wnt/β-catenin axis in CRC plays an imperative role in regulating metastasis and autophagy in vivo ( Liu et al, 2019 ).…”

The Roles of microRNA miR-185 in Digestive Tract Cancers

“…miR-185 upregulation reduced aggressive features of CRC by directly targeting WNT1 as well as MYC and CCND1 further downstream [ 98 , 99 ]. Urothelial carcinoma-associated 1 (UCA1) is an lncRNA that is significantly upregulated in CRC and involved in its progression [ 100 ]. UCA1 functions as a sponge for miR-185-5p, thereby activating the WNT1-inducible signaling pathway protein 2 (WISP2)/β-catenin pathway and promoting CRC.…”