1. Academic Validation
  2. Long non-coding RNA linc00659 promotes tumour progression by regulating FZD6/Wnt/β-catenin signalling pathway in colorectal cancer via m6A reader IGF2BP1

Long non-coding RNA linc00659 promotes tumour progression by regulating FZD6/Wnt/β-catenin signalling pathway in colorectal cancer via m6A reader IGF2BP1

  • J Gene Med. 2023 Nov 27:e3636. doi: 10.1002/jgm.3636.
Shufen Xu 1 Zichun Liu 1 Qian Luo 1 Lisha Chang 1 Jie Ding 1 Yanan Xiao 1 Yangyang Zhang 2 Guoren Zhou 3 Keming Wang 1
Affiliations

Affiliations

  • 1 Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
  • 2 Department of General Medical, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
  • 3 Department of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Abstract

Background: Abnormal N6-methyladenosine (m6A) modification has become a driving factor in tumour development and progression. The linc00659 is abnormally highly expressed in digestive tract tumours and promotes Cancer progression, but there is little research on the mechanism of linc00659 and m6A.

Methods: The expression of linc00659 in colorectal Cancer (CRC) tissues and cells was assessed by a quantitative Real-Time PCR. The proliferative capacity of CRC cells was determined by colony formation, Cell Counting Kit-8 and 5-ethynyl-2 deoxyuridine assays, and the migratory capacity of CRC was determined by wound healing and transwell assays and tube formation. In vivo, a xenograft tumour model was used to detect the effect of linc00659 on tumour growth. The Wnt/β-catenin signalling pathway and related protein expression levels were measured by western blotting. The binding of linc00659 to insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) was assessed by RNA pull-down and an immunoprecipitation assay. The effect of IGF2BP1 on FZD6 was detected by an RNA stability assay.

Results: The expression of linc00659 was abnormally elevated in CRC tissues and cells compared to normal colonic tissues and cells. We confirm that linc00659 promotes the growth of CRC cells both in vivo and in vitro. Mechanistically, linc00659 binds to IGF2BP1 and specifically enhances its activity to stabilize the target gene FZD6. Therefore, linc00659 and IGF2BP1 activate the Wnt/β-catenin signalling pathway, promoting cell proliferation in CRC.

Conclusions: Our results show that linc00659 and IGF2BP1 cooperate to promote the stability of the target FZD6 mRNA, thereby facilitating CRC progression, which may represent a potential diagnostic, prognostic and therapeutic target for CRC.

Keywords

FZD6; IGF2BP1; Wnt/β-catenin pathway; colorectal cancer; linc00659.

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