Dataset Information

SMC1A regulated by KIAA1429 in m6A-independent manner promotes EMT progress in breast cancer.

ABSTRACT: As a component of N6-methyladenosine (m6A) "writers," KIAA1429 was reported to promote breast cancer proliferation and growth in m6A-independent manners. However, the related mechanism of KIAA1429 in breast cancer metastasis has not been reported. In the present study, we found KIAA1429 could significantly promote the migration and invasion of breast cancer cells. Then we demonstrated that knockdown of KIAA1429 could impede breast cancer metastasis in nude mice in vivo. The level of SNAIL expression and epithelial-mesenchymal transition (EMT) progress was positively related with KIAA1429. Furthermore, we confirmed that the suppression of cell migration, invasion, and EMT progress by knockdown of KIAA1429 could be reversed by the upregulation of SNAIL. However, structural maintenance of chromosomes 1A (SMC1A), not KIAA1429, bound with the SNAIL promoter region directly and promoted the transcription of SNAIL. Then we confirmed that KIAA1429 could bind to the motif in the 3' UTR of SMC1A mRNA directly and enhance SMC1A mRNA stability. In conclusion, our study revealed a novel mechanism of the KIAA1429/SMC1A/SNAIL axis in the regulation of metastasis of breast cancer. Moreover, it first provided detailed investigation of how KIAA1429 regulated the targeted gene expression at posttranscriptional levels as an RNA binding protein unrelated to its m6A modification.

SUBMITTER: Zhang X

PROVIDER: S-EPMC8683616 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

SMC1A regulated by KIAA1429 in m6A-independent manner promotes EMT progress in breast cancer.

Zhang Xu X Dai Xin-Yuan XY Qian Jia-Yi JY Xu Feng F Wang Zhang-Wei ZW Xia Tian T Zhou Xu-Jie XJ Li Xiao-Xia XX Shi Liang L Wei Ji-Fu JF Ding Qiang Q

Molecular therapy. Nucleic acids 20210819

As a component of N6-methyladenosine (m6A) "writers," KIAA1429 was reported to promote breast cancer proliferation and growth in m6A-independent manners. However, the related mechanism of KIAA1429 in breast cancer metastasis has not been reported. In the present study, we found KIAA1429 could significantly promote the migration and invasion of breast cancer cells. Then we demonstrated that knockdown of KIAA1429 could impede breast cancer metastasis in nude mice <i>in vivo</i>. The level of SNAIL ...[more]

PMID: 34976433

Similar Datasets

Project description:BackgroundN6-methyladenosine (m6A) is the most common post-transcriptional modification at the RNA level. However, the exact molecular mechanisms of m6A epigenetic regulation in breast cancer remain largely unknown and need to be fully elucidated.Methods The integrating bioinformatics analyses were used to screen clinical relevance and dysregulated m6A "reader" protein YTHDF1 in breast cancer from TCGA databases, which was further validated in a cohort of clinical specimens. Furthermore, functional experiments such as the CCK-8 assay, EdU assay, wound healing assay, transwell invasion assay and cell cycle assay were used to determine the biological role of YTHDF1 in breast cancer. RIP, m6A-IP, and CLIP assays were used to find the target of YTHDF1 and further verification by RT-qPCR, western blot, polysome profiling assay. The protein-protein interaction between YTHDF1 and FOXM1 was detected via co-immunoprecipitation.ResultsOur study showed that YTHDF1 was overexpressed in breast cancer cells and clinical tissues specimens. At the same time, the high expression level of YTHDF1 was positively correlated with tumor size, lymph node invasion, and distant metastasis in breast cancer patients. YTHDF1 depletion repressed the proliferation, invasion and epithelial-mesenchymal transformation (EMT) and induced G0/G1 phase cell cycle arrest of breast cancer cells in vitro and in vivo. We also demonstrated that FOXM1 is a target of YTHDF1. Through recognizing and binding to the m6A-modified mRNA of FOXM1, YTHDF1 accelerated the translation process of FOXM1 and promoted breast cancer metastasis. Whereas overexpression of FOXM1 in breast cancer cells partially counteracted the tumor suppressed effects caused by YTHDF1 silence, which further verified the regulatory relationship between YTHDF1 and FOXM1.ConclusionOur study reveals a novel YTHDF1/FOXM1 regulatory pathway that contributes to metastasis and progression of breast cancer, suggesting that YTHDF1 might be applied as a potential biomarker and therapeutic target. That also advances our understanding of the tumorigenesis for breast cancer from m6A epigenetic regulation.

Dataset Information

SMC1A regulated by KIAA1429 in m6A-independent manner promotes EMT progress in breast cancer.

Publications

SMC1A regulated by KIAA1429 in m6A-independent manner promotes EMT progress in breast cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets