PMID- 37096864 OWN - NLM STAT- MEDLINE DCOM- 20230707 LR - 20230707 IS - 2045-7634 (Electronic) IS - 2045-7634 (Linking) VI - 12 IP - 12 DP - 2023 Jun TI - Visinin-like 1, a novel target gene of the Wnt/beta-catenin signaling pathway, is involved in apoptosis resistance in colorectal cancer. PG - 13426-13437 LID - 10.1002/cam4.5970 [doi] AB - BACKGROUND: Abnormal activation of Wnt/beta-catenin signaling is associated with various aspects of cancer development. This study explored the roles of novel target genes of the Wnt/beta-catenin signaling pathway in cancer cells. METHODS: Using the haploid chronic myelogenous leukemia cell line HAP1, RNA sequencing (RNA-seq) was performed to identify genes whose expression was increased by APC disruption and reversed by beta-catenin knockdown (KD). The regulatory mechanism and function of one of the candidate genes was investigated in colorectal cancer (CRC) cells. RESULTS: In total, 64 candidate genes whose expression was regulated by Wnt/beta-catenin signaling were identified. Of these candidate genes, the expression levels of six were reduced by beta-catenin KD in HCT116 CRC cells in our previous microarray. One of these genes was Visinin-like 1 (VSNL1), which belongs to the neuronal calcium-sensor gene family. The expression of VSNL1 was regulated by the beta-catenin/TCF7L2 complex via two TCF7L2-binding elements in intron 1. VSNL1 KD-induced apoptosis in VSNL1-positive CRC cells. Additionally, forced expression of wild-type VSNL1, but not a myristoylation, Ca(2+) -binding, or dimerization-defective mutant, suppressed the apoptosis induced by camptothecin and doxorubicin in VSNL1-negative CRC cells. CONCLUSION: Our findings suggest that VSNL1, a novel target gene of the Wnt/beta-catenin signaling pathway, is associated with apoptosis resistance in CRC cells. CI - (c) 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. FAU - Tage, Hiroki AU - Tage H AUID- ORCID: 0009-0003-3155-0179 AD - Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. FAU - Yamaguchi, Kiyoshi AU - Yamaguchi K AUID- ORCID: 0000-0003-2113-4369 AD - Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. FAU - Nakagawa, Saya AU - Nakagawa S AUID- ORCID: 0000-0002-5893-1663 AD - Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. FAU - Kasuga, So AU - Kasuga S AUID- ORCID: 0000-0002-4199-9549 AD - Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. FAU - Takane, Kiyoko AU - Takane K AUID- ORCID: 0000-0002-2467-1509 AD - Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. FAU - Furukawa, Yoichi AU - Furukawa Y AUID- ORCID: 0000-0003-0462-8631 AD - Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. FAU - Ikenoue, Tsuneo AU - Ikenoue T AUID- ORCID: 0000-0001-8264-2573 AD - Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230425 PL - United States TA - Cancer Med JT - Cancer medicine JID - 101595310 RN - 0 (beta Catenin) RN - 0 (visinin) RN - 0 (VSNL1 protein, human) RN - 0 (Neurocalcin) SB - IM MH - Humans MH - Apoptosis/genetics MH - beta Catenin/genetics/metabolism MH - Cell Line, Tumor MH - Cell Movement MH - Cell Proliferation MH - *Colorectal Neoplasms/genetics/metabolism MH - Gene Expression Regulation, Neoplastic MH - *Wnt Signaling Pathway/genetics MH - *Neurocalcin/genetics PMC - PMC10315817 OTO - NOTNLM OT - Visinin-like 1 (VSNL1) OT - Wnt/beta-catenin signaling OT - apoptosis OT - colorectal cancer COIS- The authors have no conflict of interest to disclose. EDAT- 2023/04/25 17:42 MHDA- 2023/07/04 06:42 PMCR- 2023/04/25 CRDT- 2023/04/25 07:44 PHST- 2023/03/14 00:00 [revised] PHST- 2022/11/10 00:00 [received] PHST- 2023/04/07 00:00 [accepted] PHST- 2023/07/04 06:42 [medline] PHST- 2023/04/25 17:42 [pubmed] PHST- 2023/04/25 07:44 [entrez] PHST- 2023/04/25 00:00 [pmc-release] AID - CAM45970 [pii] AID - 10.1002/cam4.5970 [doi] PST - ppublish SO - Cancer Med. 2023 Jun;12(12):13426-13437. doi: 10.1002/cam4.5970. Epub 2023 Apr 25.