Overexpression of Long Non-Coding RNA FGF14-AS2 Inhibits Colorectal Cancer Proliferation Via the RERG/Ras/ERK Signaling
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ORIGINAL ARTICLE
Overexpression of Long Non-Coding RNA FGF14-AS2 Inhibits Colorectal Cancer Proliferation Via the RERG/Ras/ERK Signaling by Sponging microRNA-1288-3p Ruizhi Hou 1 & Yan Liu 2 & Yanzhuo Su 1 & Zhenbo Shu 1 Received: 7 April 2020 / Accepted: 23 June 2020 # Arányi Lajos Foundation 2020
Abstract Colorectal cancer remains one of most common cancer types with poor prognosis globally. Recent years, numerous studies depicted pivotal roles of lncRNAs in colorectal cancer progression. This study aimed to investigate the role of FGF14-AS2 in colorectal cancer development. FGF14-AS2 was found as a significantly downregulated lncRNA in TCGA dataset. Via RTqPCR, we confirmed the downregulation of FGF14-AS2 in collected colorectal carcinoma samples. Transfection of plasmid containing full length of FGF14-AS2 repressed cell proliferation and induced elevation of cell apoptosis in colorectal cancer cells. In addition, FGF14-AS2 overexpression inactivated MAPK/ERK signaling in cells. Bioinformatic analysis and subsequent cellbased assays showed that FGF14-AS2 sponging miR-1288-3p, an oncogenic miRNA in colorectal cancer. RERG, the regulator of Ras/ERK pathway, was predicted and verified as target gene of miR-1288. Via downregulation of miR-1288, FGF14-AS2 elevated RERG expression in colorectal cancer cells. Rescue assays indicated that FGF14-AS2 relied on regulation of RERG to control cell proliferation and apoptosis in colorectal cancer. Taken together, the current study demonstrated FGF14-AS2 as a regulator of colorectal cancer development via downregulation of miR-1288-3p and inactivation of Ras/ERK signaling. Keywords FGF14-AS2 . RERG . Colorectal cancer
Introduction Colorectal cancer is currently one of prevalent cancer types globally. In United States, there are more than 140,000 new cases according to data of 2019 [1]. In recent years, chemotherapy based on 5-fluorouracil has prolonged overall survival of patients with colorectal cancer [2]. However, due to the complexity of signaling network in colorectal cancer, colorectal cancer cells exhibited strong proliferative ability and resistance to cell apoptosis. It is imperative to discover novel targets and mechanisms for colorectal cancer development. Long non-coding RNAs (lncRNAs) are single-stranded molecules with more than 200 nucleotides in length [3].
* Zhenbo Shu [email protected] 1
Department of Gastrointestinal Colorectal Surgery, the Third Hospital of Jilin University, Jilin University, Changchun, Jilin 130033, China
2
Department of Ultrasound, the Third Hospital of Jilin University, Jilin University, Changchun, Jilin 130033, China
According to competing endogenous RNA (ceRNA) hypothesis, lncRNAs interact with microRNAs (miRNAs) and release mRNA from miRNA binding [4]. Via sponging miRNAs, lncRNAs regulate gene expression to control many physiology processes. Aberrant expression of lncRNAs leads to disruption of signaling network and human diseases including colorectal cancer [5–7]. For example, lncRNA MALAT1 sponged miR-145 and upregulat
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