2. Academic Validation
  3. METTL3 dual regulation of the stability of LINC00662 and VEGFA RNAs promotes colorectal cancer angiogenesis

METTL3 dual regulation of the stability of LINC00662 and VEGFA RNAs promotes colorectal cancer angiogenesis

  • Discov Oncol. 2022 Sep 17;13(1):89. doi: 10.1007/s12672-022-00557-3.
Guoying Zhang 1 2,  Tianjun Wang 3,  Zihui Huang 2,  Yuanyuan Chen 4,  Li Sun 1,  Xia Xia 2,  Fang He 2,  Chenying Fan 2,  Shukui Wang 5 6,  Wanli Liu 7
Affiliations

Affiliations

  • 1 Department of General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, No. 68, Changle Road, Nanjing, 210006, Jiangsu, China.
  • 2 Department of Clinical Laboratory, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Nanjing University of Traditional Chinese Medicine, No. 179, Xiaolingwei Street, Nanjing, 210014, Jiangsu, China.
  • 3 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
  • 4 Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
  • 5 Department of General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, No. 68, Changle Road, Nanjing, 210006, Jiangsu, China. sk_wang@njmu.edu.cn.
  • 6 Jiangsu Collaborative Innovation Center on Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, China. sk_wang@njmu.edu.cn.
  • 7 Department of Clinical Laboratory, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Nanjing University of Traditional Chinese Medicine, No. 179, Xiaolingwei Street, Nanjing, 210014, Jiangsu, China. 18951768998@163.com.
PMID: 36114893 DOI: 10.1007/s12672-022-00557-3
Abstract

Purpose: The angiogenesis is among the primary factors that affect tumor recurrence and distant organ metastasis in colorectal Cancer (CRC). N6-methyladenosine (m6A) modification is one of the most common chemical modifications in eukaryotic mRNA, especially at the post-transcriptional level. Methyltransferase-like 3 (METTL3) promoting angiogenesis in a variety of tumors has been reported. However, the mechanism of how METTL3 dual-regulates the stability of long non-coding RNAs (lncRNAs) and vascular-related factor RNAs to affect angiogenesis in CRC is unclear.

Methods: 64 paired CRC and adjacent normal tissues were collected. In vitro, quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), actinomycin assay, methylated RNA immunoprecipitation (MeRIP) experiment,3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and colony formation assay were performed. The functions were also studied in zebrafish model Animals in vivo.

Results: We found that the vascular endothelial growth factor A(VEGFA), METTL3 and LINC00662 RNAs were highly expressed in CRC, and that METTL3 was significantly positively correlated with LINC00662 and VEGFA. The protein expression levels of CD31, CD34, VEGFA, m6A and METTL3 were all significantly increased in the CRC tissues. The angiogenesis experiments both in vivo and in vitro found that METTL3 and LINC00662 promoted angiogenesis in CRC. The actinomycin assay indicated that METTL3 maintained the stability of LINC00662 and VEGFA RNAs. In addition, the MeRIP experiment confirmed that the LINC00662 and VEGFA RNAs had METTL3-enriched sites.

Conclusion: These findings suggest that METTL3 and LINC00662 may both serve as diagnostic and prognostic predictive biomarkers for CRC and potential targets for anti-vascular therapy.

Keywords

Colorectal cancer angiogenesis; LINC00662; METTL3; N6-methyladenosine (m6A); VEGFA.

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