Abstract
Background Long noncoding RNAs (lncRNAs) are an important subtype of noncoding RNAs (ncRNAs) and microRNA sponges regulate protein-coding gene expression. The lncRNA prostate androgen-regulated transcript 1 (PART1) was implicated in the process of several cancer pathogeneses. However, studies on the regulation of PART1 expression and its mechanism in liver cancer are lacking. Methods qRT-PCR and western blot were used to detect PART1 levels in liver cancer serums and cell lines. Cell proliferation, migration, and invasion were detected using CCK8 assays, cell clones, and transwell assays. Interaction between PART1 and miR-3529-3p and forkhead box protein C2 (FOXC2) was confirmed using dual-luciferase reporter assays. Results We revealed that expression levels of PART1 and FOXC2 are significantly upregulated and the miR-3529-3p expression level significantly decreases in the serum while high expression level of PART1 is positively associated with tumour size, BCLC stage, and TNM stage. shRNA of PART1 can significantly reduce the ability of cell migration and invasion by regulating AKT signalling associated with the reduction of MMP-2 and MMP-9 protein expression. Dual-luciferase reporter assays showed that PART1 can sponge miR-3529-3p, which targets FOXC2 in liver cancer cells. The promoting or suppressing effect of PART1 for Hep3B cell proliferation, invasion, and migration is revised by miR-3529-3p mimics and inhibitors. Conclusion Results showed that downregulation of PART1 can partially inhibit proliferation and differentiation by targeting hsa-miR-3529-3p/FOXC2 axis.
Highlights
Long noncoding RNAs are an important subtype of noncoding RNAs and are ubiquitous in organisms despite their lack of protein-encoding abilities [1]
A previous study indicated that Long noncoding RNAs (lncRNAs) are an important section in competitive endogenous RNA [2, 3]. lncRNAs play key roles or pivotal functions in processes of tumour-related tumour formation, including proliferation, invasion, and metastasis [4,5,6]. e lncRNA prostate androgen-regulated transcript 1 (PART1) can regulate the proliferation and apoptosis of prostate cancer cells [7]
Erefore, we selected Hep3B cells for subsequent experiments. e clinical results showed that PART1 is significantly overexpressed in liver cancer (Table 1), thereby indicating that PART1 is unrelated to gender, age, and metastasis of liver cancer but related to tumour size, TNM stage, and BCLC stage
Summary
Long noncoding RNAs (lncRNAs) are an important subtype of noncoding RNAs (ncRNAs) and microRNA sponges regulate protein-coding gene expression. e lncRNA prostate androgen-regulated transcript 1 (PART1) was implicated in the process of several cancer pathogeneses. Studies on the regulation of PART1 expression and its mechanism in liver cancer are lacking. QRT-PCR and western blot were used to detect PART1 levels in liver cancer serums and cell lines. Interaction between PART1 and miR-3529-3p and forkhead box protein C2 (FOXC2) was confirmed using dual-luciferase reporter assays. ShRNA of PART1 can significantly reduce the ability of cell migration and invasion by regulating AKT signalling associated with the reduction of MMP-2 and MMP-9 protein expression. Dual-luciferase reporter assays showed that PART1 can sponge miR-3529-3p, which targets FOXC2 in liver cancer cells. E promoting or suppressing effect of PART1 for Hep3B cell proliferation, invasion, and migration is revised by miR-3529-3p mimics and inhibitors. Results showed that downregulation of PART1 can partially inhibit proliferation and differentiation by targeting hsa-miR-3529-3p/FOXC2 axis
Published Version
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