Open Access

Hsa_circ_0038646 promotes cell proliferation and migration in colorectal cancer via miR‑331‑3p/GRIK3

  • Authors:
    • Haipeng Du
    • Zhiguo He
    • Fumei Feng
    • Daming Chen
    • Lei Zhang
    • Jingzhen Bai
    • Huiguo Wu
    • Enkun Han
    • Jiansheng Zhang
  • View Affiliations

  • Published online on: April 21, 2020     https://doi.org/10.3892/ol.2020.11547
  • Pages: 266-274
  • Copyright: © Du et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Increasing evidence supports the essential roles of circular RNAs (circRNAs) and microRNAs (miRNAs/miRs) in different types of human cancer. For example, hsa_circ_0137008 functions as a sponge for mi‑338‑5p and inhibits the malignant phenotype in colorectal cancer. Furthermore, hsa_circ_RNA_0011780 downregulates FBXW7 by targeting miR‑554a and suppressing the progression of non‑small cell lung cancer. Thus far, only a single report has identified that the miRNA miR‑331‑3p exerts a pivotal effect on human colorectal cancer (CRC) evolution. However, both the up‑ and downstream regulatory mechanisms of miR‑331‑3p are unclear. In the present study, it was predicted via bioinformatics analysis that the circRNA, hsa_circ_0038646, and the glutamate receptor ionotropic kainate 3 (GRIK3) gene contain binding sites that can interact with miR‑331‑3p. Thus, hsa_circ_0038646/miR‑331‑3p/GRIK3 may be a novel therapeutic pathway for CRC. Reverse transcription‑quantitative PCR and western blotting analyses were performed, as well as cell proliferation, luciferase reporter and Transwell migration assays. Hsa_circ_0038646 was overexpressed in both CRC cells and tissues, and this aberrant expression was positively related with increasing tumor grade. Knockdown of hsa_circ_0038646 significantly weakened human CRC cell proliferation and migration. It was shown that hsa_circ_0038646 can sponge miR‑331‑3p to suppress its expression, and that suppression of miR‑331‑3p can reverse the effects of hsa_circ_0038646 inhibition in CRC cells. It was determined that GRIK3 is a downstream target of miR‑331‑3p, and that hsa_circ_0038646 could increase the levels of GRIK3 by suppressing miR‑331‑3p in CRC cells. Restoring GRIK3 expression rescued the weakened CRC cell proliferation and migration following hsa_circ_0038646 knockdown. The present study indicated that hsa_circ_0038646 functions as a tumor promoter in CRC by increasing GRIK3 expression via sponging of miR‑331‑3p. The hsa_circ_0038646/miR‑331‑3p/GRIK3 axis may be a novel therapeutic and diagnostic target of CRC.

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July 2020
Volume 20 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

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APA
Du, H., He, Z., Feng, F., Chen, D., Zhang, L., Bai, J. ... Zhang, J. (2020). Hsa_circ_0038646 promotes cell proliferation and migration in colorectal cancer via miR‑331‑3p/GRIK3. Oncology Letters, 20, 266-274. https://doi.org/10.3892/ol.2020.11547
MLA
Du, H., He, Z., Feng, F., Chen, D., Zhang, L., Bai, J., Wu, H., Han, E., Zhang, J."Hsa_circ_0038646 promotes cell proliferation and migration in colorectal cancer via miR‑331‑3p/GRIK3". Oncology Letters 20.1 (2020): 266-274.
Chicago
Du, H., He, Z., Feng, F., Chen, D., Zhang, L., Bai, J., Wu, H., Han, E., Zhang, J."Hsa_circ_0038646 promotes cell proliferation and migration in colorectal cancer via miR‑331‑3p/GRIK3". Oncology Letters 20, no. 1 (2020): 266-274. https://doi.org/10.3892/ol.2020.11547