Long Non-Coding RNA CBR3-AS1 Promotes Stem-Like Properties and Oxaliplatin Resistance of Colorectal Cancer by Sponging miR-145-5p

Abstract

Background: Accumulating evidence has shown that long non-coding RNAs (lncRNAs) serve as essential regulators in a plethora of human cancers. In this study, we analyzed the expression profile and functional role of lncRNA CBR3-AS1 in colorectal cancer (CRC).Methods: CRC tissues and paired adjacent normal tissues were obtained from 133 patients. The expression levels of CBR3-AS1 and miR-145-5p in tissues and cells were detected by RT-qPCR analysis. The proliferation, oxaliplatin resistance, apoptosis, migration, invasion and stem-like properties of CRC cells were detected by MTT assay, flow cytometry analysis, transwell assay and mammosphere formation assay, respectively. Western blot analysis was performed to detect the expression levels of relevant proteins. Dual-luciferase reporter assay and RNA immunoprecipitation assay verified the direct interaction between CBR3-AS1 and miR-145-5p in CRC.Results: High expression levels of CBR3-AS1 were found in CRC tissues and cell lines. Upregulated CBR3-AS1 was closely associated with poor prognosis and adverse clinicopathological features of CRC patients. Artificial knockdown of CBR3-AS1 markedly suppressed the proliferation, migration, invasion and stem-like properties, but promoted the apoptosis of CRC cells. Moreover, we observed that CBR3-AS1 could directly bind to miR-145-5p and negatively regulated its expression in CRC. Further experiments also demonstrated that inhibition of miR-145-5p reverted the effects of CBR3-AS1 knockdown on CRC cells. In addition, compared with the parental cells, CBR3-AS1 expression was strikingly increased in oxaliplatin-resistant CRC cells, and the oxaliplatin resistance was notably diminished by CBR3-AS1 knockdown. Conclusions: To conclude, our study suggested that CBR3-AS1 serves an oncogenic role in CRC, and may be exploited as a novel therapeutic target for CRC patients.

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

“…Compared to the parental cells, miR-145-5p expression was also decreased in OXA resistant CRC cells. It was concluded that the data collected was convincing enough to show that CBR3-AS1 promotes stem-like properties and OXA resistance in CRC cells by sponging miR-145-5p [257]. Another recent study demonstrated that lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was upregulated in OXA resistant CRC, while its deficiency resulted in enhanced OXA sensitivity in the resistant cells [258].…”

“…In another recent study, the lncRNA CBR3-AS1 was overexpressed in OXA resistant CRC cells, and upon knockdown of this lncRNA, it significantly enhanced OXA sensitivity in the resistant cells [257]. Xi et al provided evidence that this lncRNA acts as an miR-145-5p sponge and through this interaction, it is responsible for promoting OXA resistance and stem-like properties in CRC cells [257].…”