Abstract
Long non-coding RNAs (lncRNAs) play important roles in a range of different human cancers. However, the role of lncRNA solute carrier organic anion transporter family member 4A1-AS1 (SLCO4A1-AS1) in colon cancer remains enigmatic. Hence, we aimed to explore the specific role of SLCO4A1-AS1 in colon cancer stem cells. Colon cancer-related differentially expressed lncRNA and mRNA were screened using microarray-based analysis, and the expression of SLCO4A1-AS1 and SLCO4A1 in colon cancer tissues was determined using reverse transcription quantitative polymerase chain reaction and western blot analysis. The interaction among SLCO4A1-AS1, microRNA-150-3p (miR-150-3p) and SLCO4A1 was verified using dual-luciferase reporter assay, RNA immunoprecipitation and RNA pull-down. Moreover, SLCO4A1-AS1, miR-150-3p and/or SLCO4A1 were overexpressed or depleted in colon cancer cells to detect their effects on migration, invasion, sphere formation, apoptosis and tumorigenesis abilities of colon cancer stem CD133+CD44+ cells using both in vitro and in vivo assays. SLCO4A1-AS1 and SLCO4A1 were screened as the differentially expressed lncRNA and mRNA in colon cancer tissues. SLCO4A1-AS1 was confirmed to competitively bind to miR-150-3p to elevate SLCO4A1 expression. Moreover, knockdown of SLCO4A1-AS1 decreased SLCO4A1 expression, thus inhibiting cell migration, invasion, sphere formation, and tumorigenesis abilities and enhancing the apoptosis of CD133+CD44+ cells. Collectively, these findings provide evidence demonstrating that depleting SLCO4A1-AS1 competitively binds to miR-150-3p, which downregulates SLCO4A1 expression, thus hindering colon cancer progression.This study reports that long non-coding RNA lncRNA SLCO4A1-AS1 regulates the characteristics of colon cancer stem cells. Moreover, SLCO4A1 targets miR-150-3p. LncRNA SLCO4A1-AS1 can be used as ceRNA to adsorb miR-150-3p and thus affect the expression of SLCO4A1. Mechanistically, miR-150-3p can downregulate SLCO4A1, thereby inhibiting migration, invasion, spheroidization and tumor formation of colon cancer stem cells. This study lays a theoretical foundation for in-depth understanding of the pathogenesis of colon cancer and points to new therapeutic targets.
Highlights
These authors contributed : Kun Wu, Ting Xu, Xudong Song.Colon cancer is the third most common cancer in men and the second in women, imposing high disease burden on public health [1]
Expressed long non-coding RNAs (lncRNAs) and mRNAs were obtained from the Gene Expression Profiling Interactive Analysis (GEPIA) website, and the correlation between lncRNA and mRNA was predicted via the ChIPBase v2.0 website
E SLCO4A1-AS1 and miR-150-3p binding to Argonaute 2 (Ago2) protein determined by RNA immunoprecipitation (RIP). #p < 0.05 vs. immunoglobulin G (IgG)
Summary
These authors contributed : Kun Wu, Ting Xu, Xudong Song.Colon cancer is the third most common cancer in men and the second in women, imposing high disease burden on public health [1]. The prognosis and treatment of colon cancer are mainly monitored by histologic tumor staging [2]. Known as tumor-initiating cells, are self-renewing and aggressive cells that often lead to the development and occurrence of numerous types of cancers including colon cancer [3]. Targeting cancer stem cells directly could help to enhance the diagnosis and therapy of colon cancer. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been shown to play important roles in colorectal cancer, and can be used as diagnostic markers as well as therapeutic targets [4, 5]. SLCO4A1-AS1 had been shown to be highly expressed in bladder cancer, while the downregulation of SLCO4A1-AS1 inhibited the proliferation, LncRNA SLCO4A1-AS1 modulates colon cancer stem cell properties by binding to miR-150-3p and positively
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