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Long Non-coding RNA MIR570MG Causes Regorafenib Resistance in Colon Cancer by Repressing miR-145/SMAD3 Signaling

Fang Wei1, Mofei Wang1, Zhen Li1

  • 1Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.

Frontiers in Oncology
|March 21, 2020
PubMed

Insights

Long non-coding RNA MIR570MG promotes colon cancer resistance to regorafenib by sponging miR-145, which targets SMAD3. This mechanism highlights a new therapeutic target for overcoming drug resistance in colon cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Long non-coding RNAs (lncRNAs) are implicated in cancer development, but their role in colon cancer drug resistance is not fully understood.
  • Regorafenib is a key treatment for colon cancer, yet resistance limits its efficacy.

Purpose of the Study:

  • To elucidate the mechanism by which lncRNAs contribute to regorafenib resistance in colon cancer.
  • To investigate the role of lncRNA MIR570MG in mediating resistance to regorafenib.

Main Methods:

  • Comparative analysis of lncRNA expression in regorafenib-resistant versus sensitive colon cancer cells.
  • In vitro assays including dual-luciferase reporter assays to confirm molecular interactions.
  • In vivo studies using human colon cancer mouse models (HCT116R).

Main Results:

  • MIR570MG was upregulated in regorafenib-resistant colon cancer cells and promoted resistance.
  • MIR570MG sponged miR-145, leading to decreased miR-145 levels. Overexpression of miR-145 sensitized cells to regorafenib.
  • miR-145 directly targeted SMAD3, inhibiting TGFβ/SMAD3 signaling and cell proliferation. MIR570MG overexpression reversed these effects.

Conclusions:

  • MIR570MG promotes regorafenib resistance in colon cancer by sequestering miR-145, thereby activating the SMAD3 signaling pathway.
  • Targeting the MIR570MG/miR-145/SMAD3 axis may offer a strategy to overcome regorafenib resistance in colon cancer.
Keywords:
LncRNA MIR570MGSMAD3TGFβmetastatic colon cancermiR-145regorafenibresistance

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