Knockdown of circNRIP1 sensitizes colorectal cancer to 5‑FU via sponging miR‑532‑3p

Abstract

The present study aimed to investigate the influence of circular RNA nuclear receptor-interacting protein 1 (circNRIP1) on the chemotherapeutic effect of 5-fluorouracil (5-FU) in colorectal cancer (CRC) and reveal its potential molecular mechanisms. The effects of circNRIP1 on cell proliferation, migration and invasion, and apoptosis were evaluated using Cell Counting Kit-8, Transwell and flow cytometric assays, respectively. A dual-luciferase reporter assay was performed to verify the potential interaction between circNRIP1 and microRNA (miR)-532-3p. The results of the present study indicated that circNRIP1 was upregulated in CRC and its increased expression was associated with CRC progression. Furthermore, overexpression of circNRIP1 promoted CRC cell proliferation, invasion and migration, while it inhibited apoptosis. Knockdown of circNRIP1 significantly enhanced the 5-FU-induced inhibition of the viability of HCT116 and SW480 cells. Bioinformatics analysis predicted that miR-532-3p was a direct target of circNRIP1, which was further confirmed by a dual-luciferase reporter assay. miR-532-3p silencing reversed the effects of circNRIP1 knockdown on the sensitivity of 5-FU in the chemotherapy of CRC. The results suggested that circNRIP1 and miR-532-3p may be utilized to improve the diagnosis of CRC and serve as diagnostic markers. In conclusion, overexpression of circNRIP1 promoted the progression of CRC, while circNRIP1 silencing sensitized CRC cells to 5-FU via sponging miR-532-3p.

Systematic analysis of circRNA biomarkers for diagnosis, prognosis and therapy in colorectal cancer

“…Among them, 19 were related to lymph node metastasis, 10 were related to distant metastasis, seven were related to both lymph node metastasis and distant metastasis, and the remaining six were related to liver metastasis ( Supplementary Table S7 ). There were 13 circRNAs associated with drug resistance, of which circDDX17 ( Ren et al, 2020 ), circ_0007031 ( He et al, 2020 ), circ_0032833 ( Li and Zheng, 2020 ), circ_0000338 ( Zhao et al, 2021 ), circNRIP1 ( Liu et al, 2021 ) were associated with 5-fluorouracil resistance; circ_0005963 ( Wang et al, 2020c ), circFBXW7 ( Xu et al, 2021 ) were associated with oxaliplatin resistance; circ_0000338 ( Hon et al, 2019 ), circ_32883 ( Abu et al, 2019 ) were associated with both 5-fluorouracil and oxaliplatin; circ_ 0020095 ( Sun et al, 2020 ), circ_0071589 ( Zhang et al, 2021b ), and circ_0131,663 ( Wang et al, 2021 ) were associated with cisplatin resistance; circCSPP1 ( Xi et al, 2021 ), and circ_0006174 ( Zhang et al, 2022 ) were associated with Adriamycin resistance. In addition, circ_0001313 was associated with radiotherapy resistance ( Wang et al, 2019a ) ( Supplementary Table S7 ).…”

Circ‐ERBB2 knockdown sensitized colorectal cancer cells to 5‐FU via miR‐181a‐5p/PTEN/Akt pathway

“…Consistent with our study, many articles verify the influence of circRNAs dysregulation on CRC cell sensitivity to 5‐FU and enhances drug resistance. [ 29,30 ] For example, one study found that circ‐0000338 enhances 5‐FU resistance in CRC by negatively regulating miRNAs. [ 29 ] Another study found that circNRIP1 silencing sensitizes HCT116 and SW480 cells to 5‐FU by negatively regulating miR‐532‐3p.…”

“…[ 29 ] Another study found that circNRIP1 silencing sensitizes HCT116 and SW480 cells to 5‐FU by negatively regulating miR‐532‐3p. [ 30 ]…”

“…[29] Another study found that circNRIP1 silencing sensitizes HCT116 and SW480 cells to 5-FU by negatively regulating miR-532-3p. [30] As revealed by miRNA sponge hypothesis, circRNA-miRNA-mRNA regulatory network modulates the levels of target genes via ncRNA transcripts. [22] Previous studies have found that circ-ERBB2 inhibiting circ-ERBB2 expression.…”

The Crosstalk and Clinical Implications of CircRNAs and Glucose Metabolism in Gastrointestinal Cancers

“…Furthermore, circRNAs are associated with drug resistance. In CRC, circNRIP1 [ 46 ] and circ_0000338 [ 47 ] confer 5-fluorouracil (5-FU) resistance and contribute to CRC progression, whereas circ_0082182 [ 48 ], hsa_circ_0005963 [ 49 ] and circATG4B [ 50 ] confer resistance to oxaliplatin.…”