Abstract
In this study, we intended to figure out the biological significance of long non-coding RNAs (lncRNAs) solute carrier organic anion transporter family member 4A1 antisense RNA 1 (SLCO4A1-AS1) in pancreatic cancer (PC). Cell counting kit-8, colony formation, wound healing, transwell, and flow cytometry experiments were performed to reveal how SLCO4A1-AS1 influences PC cell proliferation, migration, invasion, and apoptosis. Thereafter, bioinformatics analysis, RNA immunoprecipitation assay, luciferase reporter assay, and RNA pull-down assay were applied for determining the binding sites and binding capacities between SLCO4A1-AS1 and miR-4673 or kinesin family member 21B (KIF21B) and miR-4673. The results depicted that SLCO4A1-AS1 was upregulated in PC, and SLCO4A1-AS1 knockdown suppressed PC cell growth, migration, invasion, and induced cell apoptosis. Furthermore, SLCO4A1-AS1 was verified to modulate the expression of KIF21B by binding with miR-4673. SLCO4A1-AS1 exerted an oncogenic function in PC. The overexpression of SLCO4A1-AS1 aggravated the malignant behaviors of PC via the upregulation of KIF21B by sponging miR-4673. Our findings revealed a novel molecular mechanism mediated by SLCO4A1-AS1, which might play a significant role in modulating the biological processes of PC.
Highlights
Pancreatic cancer (PC) is known as a prevailing malignancy in digestive system worldwide, accounting for approximately 56,770 new cases and 45,750 deaths in America in 2019 [1]
Accumulating evidence has suggested that long noncoding RNAs are a type of RNA transcripts in eukaryotic cells longer than 200 nucleotides defined by a lack of protein-coding potential [7]
Despite new technologies and therapies for early diagnosis, most patients are still diagnosed at an advanced stage for the insidious onset of this disease [20]
Summary
Pancreatic cancer (PC) is known as a prevailing malignancy in digestive system worldwide, accounting for approximately 56,770 new cases and 45,750 deaths in America in 2019 [1]. More and more studies have revealed the regulation of lncRNAs in a range of biological processes, involving cell growth, apoptosis, migration, and invasion in almost all human cancers, including gastric cancer, hepatocellular carcinoma, and prostate cancer [8,9,10,11]. LncRNA solute carrier organic anion transporter family member 4A1 antisense RNA 1 (SLCO4A1AS1) was verified to be an oncogene in some cancers [12]. In non-small-cell lung cancer, SLCO4A1-AS1 facilitates cellular processes by mediating the miR-223-3p/ IKKα/NF-κB signaling [13]. SLCO4A1AS1 accelerates cell growth and migration via β-catenindependent Wnt pathway [14]. SLCO4A1-AS1 binds with miR-335-5p to elevate organic cation/carnitine transporter (OCT4) expression, aggravating malignant phenotypes of bladder cancer [15].
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