<p>LncRNA NEAT1 Regulates 5-Fu Sensitivity, Apoptosis and Invasion in Colorectal Cancer Through the MiR-150-5p/CPSF4 Axis</p>

Abstract

Background Colorectal cancer (CRC) is one of the most prevalent malignancies in the world. Long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) is involved in the development of many cancers. However, its role and mechanism in CRC progression still need further exploration. Methods The expression levels of lnc-NEAT1, microRNA-150-5p (miR-150-5p) and cleavage and polyadenylation specific factor 4 (CPSF4) were determined by quantitative real-time PCR (qRT-PCR). The sensitivity of cells to 5-fluorouracil (5-Fu) was measured by 3-(4,5-dimethyl-2 thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Cell apoptosis and invasion were evaluated by flow cytometry and transwell assays, respectively. Western blot (WB) analysis was used to assess the levels of resistance-related proteins and CPSF4 protein. Besides, dual-luciferase reporter assay was used to verify the interactions among lnc-NEAT1, miR-150-5p and CPSF4. Also, mice xenograft models were used to determine the effect of lnc-NEAT1 on CRC tumor growth in vivo. Results In CRC, the expression of lnc-NEAT1 was upregulated and miR-150-5p was downregulated, and the expression of both was negatively correlated. Silencing of lnc-NEAT1 promoted the 5-Fu sensitivity, enhanced the apoptosis and suppressed the invasion of CRC cells. MiR-150-5p could be sponged by lnc-NEAT1, and its inhibitors could partially reverse the effect of lnc-NEAT1 silencing on CRC progression. Besides, CPSF4 could be targeted by miR-150-5p, and its overexpression also could invert the effect of lnc-NEAT1 knockdown on CRC progression. Further, CPSF4 expression was regulated by lnc-NEAT1 and miR-150-5p. In addition, interference of lnc-NEAT1 reduced tumor volume and improved the sensitivity of CRC to 5-Fu in vivo. Conclusion Lnc-NEAT1 acted as an oncogene in CRC through regulating CPSF4 expression by sponging miR-150-5p. The discovery of lnc-NEAT1/miR-150-5p/CPSF4 axis provided a novel approach for CRC genomic therapy strategy.

The Mechanistic Roles of ncRNAs in Promoting and Supporting Chemoresistance of Colorectal Cancer

“…Another research group monitored the expression of NEAT1 in 5-FU resistance CRC cells [224]. Wang et al were the first to indicate that NEAT1 could regulate 5-FU sensitivity in CRC via the miR-150-5p/Cleavage and Polyadenylation Specific Factor 4 (CPSF4) axis [224].…”

“…Another research group monitored the expression of NEAT1 in 5-FU resistance CRC cells [224]. Wang et al were the first to indicate that NEAT1 could regulate 5-FU sensitivity in CRC via the miR-150-5p/Cleavage and Polyadenylation Specific Factor 4 (CPSF4) axis [224]. The data proved that NEAT1 and miR-150-5p expression was negatively correlated (upregulated and downregulated, respectively) in CRC tissues and cells [224].…”

Identification of Novel Survival Related lncRNA-miRNA-mRNA Competing Endogenous RNA Network Associated with Immune Infiltration in Colorectal Cancer

“…NEAT1 regulates the Wnt/β-catenin signaling pathway by targeting DDX5, thereby facilitating CRC cells migration and invasion in vitro and in vivo [41]. Furthermore, NEAT1 also has been found to participate in chemoresistance of CRC, NEAT1 knockdown increased the sensitivity of 5-uorouracil and promoted apoptosis in CRC cells [42]. These studies above improved the reliability of our research that dysregulation of lncRNA XIST and NEAT1 was closely correlated with the pathogenesis of CRC, which is valuable for further study.…”

What Is Known about Theragnostic Strategies in Colorectal Cancer

“…Both classes of ncRNAs regulate multiple cellular processes such as growth, development, and differentiation showing to be crucial for cancer initiation, progression, and dissemination and can be found in serum or other body fluids bound to protein or lipid complexes, or more frequently inside extracellular vescicles (i.e., exosomes) [ 46 ]. Furthermore, these elements seem to be strongly associated with the development of drug resistance in CRC [ 47 , 48 , 49 , 50 ]. For these reasons, miRNA and lncRNAs could have potential application in diagnosis, prognosis, and treatment of CRC.…”

“…The upregulation of LncRNA NEAT1 acts as an oncogene in CRC through the regulation of CPSF4 expression, sponging miR-150-5p. The upregulation of NEAT1 ultimately results in 5-FU resistance, suppressed apoptosis, and enhanced invasion of CRC [ 49 ]. A recent systematic review and meta-analysis of 39 studies including 2822 CRC patients consistently showed that multiple miRNAs (almost 60) could act as clinical predictors of chemoresistance and sensitivity for a combination of 14 drugs, including 5-FU and oxaliplatin.…”