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. 2020 May;24(9):5021-5027.
doi: 10.1111/jcmm.15122. Epub 2020 Apr 3.

Hsa_circ_0079662 induces the resistance mechanism of the chemotherapy drug oxaliplatin through the TNF-α pathway in human colon cancer

Mingfen Lai  1 , Guiju Liu  2 , Ruijun Li  2 , Hua Bai  2 , Jizhi Zhao  2 , Peng Xiao  2 , Jiazhuan Mei  2
Affiliations

Hsa_circ_0079662 induces the resistance mechanism of the chemotherapy drug oxaliplatin through the TNF-α pathway in human colon cancer

Mingfen Lai et al. J Cell Mol Med. 2020 May.

Abstract

The aim of the study was to research the biological functions of circRNA (hsa_circ_0079662) and its underlying mechanism in colorectal cancer. Drug-resistant cell lines (HT29-LOHP, HCT116-LOHP, HCT8-LOHP) were separately dealt with oxaliplatin concentration gradient (0.1-10 μmol/L). Real-time PCR, Western blotting, dual-luciferase assay, miRNA pull-down assay, coimmunoprecipitation and ELASA were performed to explore the mechanism of chemotherapy drug oxaliplatin resistance in CRC. The results showed that the expression of hsa_circ_0079662 was increased in drug-resistant cell lines by RT-PCR. The expression of HOXA9, TRIP6, Vcam-1, VEGFC, MMP3, MMP9 and MMP14 was higher by Western blotting. Interaction between HOXA9 and TRIP6 in CO-IP detection. Additionally, the cytokines TNF-α, IL-1 and IL-6 were also found. In conclusion, hsa_circ_0079662, as a ceRNA binding with hsa-mir-324-5p, can regulate target gene HOXA9 and induced the mechanism of chemotherapy drug oxaliplatin resistance in CRC through the TNF-α pathway in human colon cancer.

Keywords: HOXA9; Hsa_circ_0079662; TNF-α pathway; ceRNA; colorectal cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Hsa_circ_0079662 is up‐regulated in drug‐resistant CRC cell lines
Figure 2
Figure 2
Hsa_circ_0079662 promotes growth of drug‐resistant CRC cell lines
Figure 3
Figure 3
Hsa_circ_0079662 in hsa‐mir‐324‐5p treated cells, significantly reversed the growth‐inhibitory role. ****P < .001
Figure 4
Figure 4
Hsa‐mir‐324‐5p treatment decreased cell growth of cells. *P < .05
Figure 5
Figure 5
The expression of cytokines TNF‐α, IL‐1 and IL‐6 was increased in drug‐resistant CRC. *P < .05
See this image and copyright information in PMC

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