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Updated: Nov 17, 2025
Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
M6A modification of circNSUN2 promotes colorectal liver metastasis
Rong-Zhang He1,2, Jing Jiang2,3, Di-Xian Luo2,3
1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, 410078, PR China.
Abstract:
Circular RNAs (circRNAs) are playing emerging role in the pathogenesis of cancers, but the mechanisms still unknown. In the recent issue of the Nature Communications, Chen and colleagues have demonstrated that YTHDC1 facilitates N6-methyladenosine modified circNSUN2 cytoplasmic export and the circNSUN2/IGF2BP2/HMGA2 complex stabilizes HMGA2 to promote colorectal liver metastasis. These discoveries not only expand our understanding of circRNAs biology in tumor, but also demonstrate that m6A modification plays a key role for circRNAs in RNA metabolism. Therefore, these findings indicate that circRNAs may be a new approach for therapeutic target of cancers.
Insights
Circular RNAs (circRNAs) facilitate colorectal liver metastasis by exporting modified circNSUN2, stabilizing HMGA2. This reveals a key role for m6A modification in circRNA metabolism and cancer progression.
Area of Science:
- Molecular Biology
- Oncology
- RNA Biology
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer pathogenesis.
- The specific mechanisms by which circRNAs contribute to cancer, particularly metastasis, remain largely unknown.
- N6-methyladenosine (m6A) modification is a crucial epitranscriptomic mark influencing RNA metabolism and function.
Purpose of the Study:
- To elucidate the role of YTHDC1 and m6A modification in the function of circRNAs in cancer.
- To investigate the involvement of circNSUN2 in colorectal liver metastasis.
- To identify molecular mechanisms linking circRNAs to cancer progression and RNA metabolism.
Main Methods:
- Investigated the interaction between YTHDC1, circNSUN2, and downstream effectors.
- Analyzed the role of m6A modification in the cytoplasmic export of circNSUN2.
- Studied the formation of the circNSUN2/IGF2BP2/HMGA2 complex and its impact on HMGA2 stability.
Main Results:
- YTHDC1 was shown to facilitate the cytoplasmic export of N6-methyladenosine modified circNSUN2.
- The circNSUN2/IGF2BP2/HMGA2 complex was identified, which stabilizes HMGA2.
- Stabilization of HMGA2 by this complex promotes colorectal liver metastasis.
Conclusions:
- circRNAs, specifically circNSUN2, play a significant role in promoting colorectal liver metastasis.
- m6A modification is critical for circRNA function in RNA metabolism and cancer.
- circRNAs represent a potential new therapeutic target for cancer treatment.
