LINC01296/miR-141-3p/ZEB1-ZEB2 axis promotes tumor metastasis via enhancing epithelial-mesenchymal transition process

Abstract

Tumor metastasis seriously affects the survival of patients. In recent years, some studies confirmed that long non-coding RNA (lncRNA) played an essential role in tumor progression. A few studies reported that LINC01296 acted as an oncogenic regulator of cancer. However, its in-depth specific biological mechanism in tumor metastasis is still unknown. Methods: Real-time quantitative PCR (qPCR) was performed to detect the expression of LINC01296 and miR-141-3p in NSCLC, CRC tissues and cell lines, and the dual luciferase report was used to evaluate the relationship between LINC01296, miR-141-3p and ZEB1/ZEB2 relationship. Western blot experiments are used to detect changes in protein levels. Transwell and wound healing measures migration and invasion capabilities. Results: In this study, we used non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) as the research objects, LINC01296 was found to be highly expressed in NSCLC and CRC tissues and positively related to poor prognosis. We also demonstrated LINC01296 regulated NSCLC and CRC invasion and metastasis by modulating epithelial-mesenchymal transition (EMT) by up-regulating ZEB1 and ZEB2. Consequently, LINC01296 acted as a sponge of miR-141-3p, which negatively regulates EMT process. Conclusions: The report revealed a new mechanism by which LINC01296 regulates the EMT process through miR-141-3p/ZEB1-ZEB2 axis and affects cancer metastasis.

Discovery and Validation of Clinically Relevant Long Non-Coding RNAs in Colorectal Cancer

“…Information on this gene available at the Genecards website suggests that LINC01296 is poorly conserved (there are no described orthologs or paralogs), is located in a highly variable region, and is moderately expressed in only six human tissues, which are as follows: white blood cells, lymph nodes, heart, skeletal muscle, adipocyte and kidney [ 81 ]. Several studies have explored the expression of LINC01296 in CRC tissues, cell lines (SW480, SW620, LoVo, HT29, DLD1, HCT116, HCT-8, HCT-8/5-FU) and in vivo rodent models, and have shown overexpression of this lncRNA in tumoral samples compared with matching adjacent tissues [ 80 , 82 , 83 ]. Additionally, these same studies have shown a significant association with the overexpression of LINC01296 and tumor stage, lymph node metastasis, distant metastasis, as well as poor clinical prognosis and chemoresistance.…”

“…Mechanistically, the LINC01296 transcript functions as an endogenous sponge of miR-26a to regulate mucin1 (MUC1) expression, catalyzed by GALNT3 , which in turn modulates the activity of the PI3K/AKT pathway, and thereby the carcinogenesis process [ 82 ]. Proposed mechanisms of action include down-regulation of p15 for proliferation, and promotion of invasion by regulating the EMT process through the miR-141-3p/ZEB1-ZEB2 axis [ 80 , 83 ].…”

Regulations of LINC0196/miR-584-5p/miR-34a-5p/TRIM59 on progression of pediatric neuroblastoma

“…As non-coding RNAs with lengths between 200 and 100,000 nt, lncRNAs play a certain role in regulating the cell cycle, cell differentiation, epigenetics, and other life activities (4). For example, large intergenic noncoding RNA 0196 (LINC0196) has been proven to promote the migration and invasion of gastric cancer, colon cancer, cholangiocarcinoma, and other cancer cells (5)(6)(7). When the LINC0196 gene is up-regulated, the ability of cancer cells to proliferate, invade, and migrate will be enhanced.…”

Circular RNA circVAPA contributes to non-small-cell lung cancer progression via miR-342-3p-dependent regulation of ZEB2

“…ZEB2 is a member of the ZEB family, and it plays an important role in regulating cell mobility [ 21 ]. Not surprisingly, accumulating evidence demonstrated that ZEB2 behaves as an oncogene through promoting the metastasis of lung cancer cells [ 22 , 23 ]. In this study, we first analyzed the expression pattern of circVAPA in NSCLC tissues and cell lines.…”