Long Noncoding RNA PVT1 Induces Autophagy Leading to Inflammation and Lung Metastasis of Colorectal Cancer

Abstract

Background: Long noncoding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) is upregulated and manifested in various cancer types. LncRNA PVT1 plays a vital role in regulating proliferation, invasion, migration, and autophagy which could promote malignant progression. However, its mechanism of clinical significance for colon cancer remains unclear. Methods: The biological behaviors of lncRNA PVT1 were explored in the present study. HCT116 cells were transfected with PVT1 siRNA (si-PVT1) or PVT1 plasmid (oe-PVT1) to establish a PVT1 deletion and overexpression model. The levels of lncRNA PVT1 were assessed in transfected colon cancer cells using qRT-PCR. Furthermore, the cell viability, scratch, and transwell assays were performed to evaluate cell proliferation, migration, and invasion at different levels of lncRNA PVT1. However, their autophagy effects were assessed by employing Immunofluorescence assay and western blot (WB). Similarly, the rate of inflammatory infiltration was determined using the enzyme-linked immunosorbent assay (ELISA) experiment. Additionally, hematoxylin and eosin (HE) staining were utilized for indicating the metastatic tumor nodules in vivo. Results: The HCT116 cells exhibited significantly higher levels of the lncRNA PVT1 compared to the normal colonic epithelial cells. Compared to the deleted cells and untreated cells, lncRNA PVT1-overexpressing cells exhibited increased cell viability and migratory capability (p < 0.05). Suppressing PVT1 expression significantly reduced PVT1 mRNA levels post-transfection, leading to a significant decrease in cell proliferation ability (p < 0.05). Consistent with the proliferation experiment, the same trend was observed in the cell migration and invasion assays. Moreover, autophagy-associated genes, including microtubule-associated protein 1 light chain 3 (LC3), beclin-1, and Autophagy Related 3 (Atg3) were significantly upregulated in the PVT1 overexpressed cells, while decreased in the siRNA-treated cells (p < 0.05). Furthermore, there were fewer small tumor nodules observed in the lncRNA PVT1 siRNA transfected mice. While the elevated presence of lncRNA PVT1 was correlated with significantly metastatic tumor nodules and much obvious inflammatory infiltration (p < 0.05). Additionally, the levels of the tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and colony stimulating factor 1 (CSF1) were remarkably elevated in the PVT1 overexpressed mice, while exhibiting a substantial reduction in the PVT1 inhibited mice (p < 0.05). Conclusion: This study unveiled the potential of lncRNA PVT1 as a target for therapeutic interventions in the management of colorectal cancer.