Long noncoding RNA CRART16 confers 5-FU resistance in colorectal cancer cells by sponging miR-193b-5p

Abstract

Background The emergence of chemoresistance to 5-fluorouracil (5-FU)-based chemotherapy is the main cause of treatment failure in advanced and metastatic colorectal cancer (CRC) patients. Long noncoding RNAs (lncRNAs) have been reported to be involved in 5-FU resistance. Previously, we first detected that lncRNA cetuximab resistance-associated RNA transcript 16 (CRART16) could contribute to cetuximab resistance by upregulating V-Erb-B2 erythroblastic leukemia viral oncogene homologue 3 (ERBB3) expression by sponging miR-371a-5p in CRC cells. The current study aimed to explore the role of CRART16 in acquired 5-FU resistance in CRC cells and its possible mechanism. Methods Quantitative real-time PCR (RT-qPCR) was used to measure the expression levels of CRART16 in a 5-FU-resistant CRC cell subline (SW620/5-FU) and the parent cell line. Lentivirus transduction was performed to establish SW620 and Caco-2 cells stably overexpressing CRART16. Cell Counting Kit-8 (CCK-8) assays and colony formation assays were applied to measure cell chemosensitivity to 5-FU. Flow cytometric and immunofluorescence staining were adopted to assess cell apoptosis induced by 5-FU. The dual-luciferase reporter assay was used to validate the direct interactions between CRART16 and miR-193b-5p and between miR-193b-5p and high-mobility group AT-hook-2 (HMGA2). The expression levels of HMGA2, apoptosis-associated proteins and p-ERK were examined by western blotting. The statistical differences within any two groups were used Student’s t test. Results CRART16 was upregulated in SW620/5-FU cells. Overexpression of CRART16 reduced the sensitivity of CRC cells to 5-FU by attenuating apoptosis. In addition, CRART16 promoted 5-FU resistance by suppressing the expression of miR-193b-5p. Furthermore, CRART16 modulated the expression of HMGA2 by inhibiting miR-193b-5p and activated the MAPK signaling pathway. Conclusions CRART16 confers 5-FU resistance in CRC cells through the CRART16/miR-193b-5p/HMGA2/MAPK pathway.

Identifying the potential transcriptional regulatory network in Hirschsprung disease by integrated analysis of microarray datasets

“…[45][46][47][48] In cancer diseases, miR-659-3p and miR-371a-5p could regulate tumor progression and were associated with chemotherapy resistance. [49][50][51][52][53] Novel research has shown that specific miRNAs in serum or plasma exosomal were identified to have good diagnostic value in HSCR. 54 55 As mentioned previously, the miRNAs identified in this study had AUC values of more than 0.8 and remained unclear so far in HSCR, which provided new cues for future biomarker study of HSCR treatment and diagnosis.…”

“…MiR-10b-5p contributed to neurodegenerative disease, diabetes with dysfunction of interstitial Cajal cells, and neuroprotection for hippocampal neuronal cells 45–48. In cancer diseases, miR-659–3p and miR-371a-5p could regulate tumor progression and were associated with chemotherapy resistance 49–53. Novel research has shown that specific miRNAs in serum or plasma exosomal were identified to have good diagnostic value in HSCR 54 55.…”

Temporal transcriptomic changes in microRNAs involved in the host immune response and metabolism during Neospora caninum infection

“…Fc gamma R-mediated phagocytosis, Toll-like receptor signaling pathway, TNF signaling pathway, TGF-β signaling pathway, MAPK signaling pathway). Of these DEmiRNAs, downregulated miR-193b-5p has been found to target HMGA2 to inhibit 5-fluorouracil-induced apoptosis through the MAPK signaling pathway [ 62 ]. Downregulated miRNA-455-3p promoted TGF-β signaling and inhibited the development of osteoarthritis by targeting PAK2 [ 63 ].…”

Epigenetic Alteration in Colorectal Cancer: Potential Diagnostic and Prognostic Implications

“…Silencing the competitive endogenous RNA CASC15 to regulate the miR-145/ABCC1 axis overcomes resistance to oxaliplatin in CRC [ 181 ]. Moreover, long non-coding RNA CRART16, acting as a ceRNA, confers 5-FU resistance to CRC cells by inhibiting miR-193b-5p and regulating HMGA2 expression, activating the MAPK signaling pathway [ 182 ]. Additionally, overexpression of CRART16 increases the proportion of CD44+/CD133+ cells and may promote resistance to cetuximab in CRC cells through the miR-371a-5p/ERBB3/MAPK pathway [ 183 ].…”