Overexpressed lncRNA LINC00893 Suppresses Progression of Colon Cancer by Binding with miR-146b-3p to Upregulate PRSS8.

ABSTRACT

Background: Long noncoding RNAs (lncRNAs) play a significant role in the progression and metastasis of various cancers. LINC00893 has been reported to exert antitumor effect on various cancers such as gastric cancer and thyroid cancer. Bioinformatics analysis also predicted that LINC00893 was downregulated in colon cancer. However, the clinical significance and regulating mechanism of LINC00893 in colon cancer remain unknown. Methods: Expression of LINC00893, miR-146b-3p, and PRSS8 was detected in colon cancer tissues and adjacent nontumor tissues by RT-qPCR, and clinical significance was analyzed by receiver operating characteristic curve. The regulatory mechanism of LINC00893, miR-146b-3p, and PRSS8 was investigated by dual luciferase reporter and RNA pull-down assays. Proliferation, migration, invasion, and apoptosis were measured in HCT116 and SW620 cells by MTT, EdU staining, wound healing, Transwell, TUNEL, and flow-cytometry assays. Moreover, the effect of LINC00893 on colon cancer progression was further evaluated in tumor-bearing mice. Results: LINC00893 and PRSS8 were significantly downregulated, while miR-146b-3p was upregulated in colon cancer tissues compared to control group. LINC00893, miR-146b-3p, and PRSS8 had significant diagnostic value with area under curve of 0.9383, 0.7300, and 0.9644, respectively. Overexpressed LINC00893 or silenced miR-146b-3p suppressed the proliferation, migration, and invasion while promoting apoptosis in colon cancer cells (HCT116, SW620). Moreover, miR-146b-3p overexpression reversed the inhibitory effect of LINC00893, while PRSS8 knockdown rescued the suppressive effect of miR-146b-3p inhibitor on malignant cell behaviors in colon cancer. Furthermore, the tumor growth in mice was significantly reduced by LINC00893 overexpression. Conclusion: LINC00893 overexpression suppressed the progression of colon cancer by binding with miR-146b-3p to upregulate PRSS8. LINC00893 and its downstream molecules miR-146b-3p and PRSS8 may serve as novel biomarkers and therapeutic targets of colon cancer, providing new treatment options and research approaches towards colon cancer.