<p>lncRNA UCA1 Contributes to 5-Fluorouracil Resistance of Colorectal Cancer Cells Through miR-23b-3p/ZNF281 Axis</p>

Abstract

The chemoresistance of 5-fluorouracil (5-FU) limited the application of chemotherapy in colorectal cancer (CRC) treatment. Herein, we aimed to uncover the potential mechanism behind the 5-FU resistance of CRC cells. Methods: The abundance of long noncoding RNA urothelial carcinoma associated 1 (lncRNA UCA1), microRNA-23b-3p (miR-23b-3p) and zinc finger protein 281 (ZNF281) was measured by quantitative real-time polymerase chain reaction (qRT-PCR) in CRC tissues and cells. Western blot was conducted to examine autophagy-related proteins, apoptosisassociated proteins and ZNF281 in CRC tissues and cells. Cell counting kit-8 (CCK8) assay was performed to detect the viability and inhibitory concentration 50% (IC50) value of 5-FU of CRC cells. The apoptosis of CRC cells was measured by flow cytometry. The binding sites between miR-23b-3p and UCA1 or ZNF281 were predicted by miRcode and Starbase software, respectively, and the combination was confirmed by dual-luciferase reporter assay and RIP assay. Murine xenograft model was established to verify the role of UCA1 on the 5-FU resistance of CRC in vivo. Results: The 5-FU resistance of CRC was positively related to the level of UCA1 and autophagy. UCA1 accelerated the 5-FU resistance of CRC cells through facilitating autophagy and suppressing apoptosis. MiR-23b-3p was a target of UCA1 in 293T and CRC cells. The knockdown of miR-23b-3p reversed the inhibitory effects of UCA1 interference on the 5-FU resistance and autophagy and the promoting impact on the apoptosis of CRC cells. ZNF281 could bind to miR-23b-3p in 293T cells. MiR-23b-3p elevated the 5-FU sensitivity through down-regulating ZNF281 in CRC cells. UCA1 interference enhanced the 5-FU sensitivity of CRC through miR-23b-3p/ZNF281 axis in vivo. Conclusion: UCA1 mediated 5-FU resistance of CRC cells through facilitating autophagy and inhibiting apoptosis via miR-23b-3p/ZNF281 axis in vivo and in vitro.

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

“…Furthermore, miR-23b-3p elevated 5-FU sensitivity via downregulation of ZNF281 in CRC cells, while UCA1 interference also enhanced 5-FU sensitivity. This study concluded that the UCA1/miR-23b-3p/ZNF281 axis mediates 5-FU resistance in CRC, under both in vivo and in vitro conditions [211].…”

“…This work thus presented the first indications for a ceRNA network having UCA1, miR-204-5p and miR-204-5p target genes in CRC resistant cells [210]. In another study, upregulated expression of UCA1 accelerated 5-FU resistance of CRC cells by suppressing apoptosis and enhancing autophagy, via the miR-23b-3p/zinc finger protein 281 (ZNF281) axis [211]. Knockdown of miR-23b-3p reversed the inhibitory effects of UCA1 interference on 5-FU resistance by inhibiting autophagy and promoting apoptotic cell death of CRC cells.…”

LncRNA UCA1 remits LPS‐engendered inflammatory damage through deactivation of miR‐499b‐5p/TLR4 axis

“…But, a handful of evidences discovered that lncRNAs function as crucial regulators participated in modulating inflammatory damage and influenced the pathogenesis of inflammation‐related ailments, including pneumonia 4–6 . LncRNA urothelial carcinoma‐associated 1 (UCA1) has been discovered to be closely associated with various tumors, and plays widespread role in tumorigenesis 7–9 . A large number of experiments have shown that UCA1 is related to inflammatory response which could exert proinflammatory function 10–12 .…”

“…[4][5][6] LncRNA urothelial carcinoma-associated 1 (UCA1) has been discovered to be closely associated with various tumors, and plays widespread role in tumorigenesis. [7][8][9] A large number of experiments have shown that UCA1 is related to inflammatory response which could exert proinflammatory function. [10][11][12] Corroborative research disclosed that UCA1 is upregulated following LPS induced sepsis in human dermal microvascular endothelial cells.…”

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.…”