Alternative ANKHD1 transcript promotes proliferation and inhibits migration in uterine corpus endometrial carcinoma

npj Genomic Medicine, 2022 · DOI: https://doi.org/10.1038/s41525-022-00321-0 · Published: August 8, 2022

Simple Explanation

Alternative splicing (AS) is a common regulatory mechanism in gene expression, which allows multiple mRNA transcripts from a single gene. Abnormal splicing may lead to aberrant biological function and result in many diseases, including some cancers. The upregulated expression of HSPB1 induced downregulation of ANKHD1-BP3 and promoted tumor metastasis.

Study Duration

Not specified

Participants

547 primary UCEC samples from the TCGA database

Evidence Level

Not specified

Key Findings

1
An alternate terminator of ANKHD1 transcripts named ANKHD1-BP3 was found to be signiﬁcantly related to metastasis and OS in UCEC and signiﬁcantly associated with HSPB1.
2
The expression levels of ANKDH1-BP3 were low in metastasis and were downregulated by HSPB1.
3
HSPB1 negatively regulates ANKHD1-BP3 and that a low level of ANKHD1-BP3 promotes cell proliferation and affects metastasis via the PI3K/AKT signaling pathway in UCEC cell lines.

Research Summary

Based on TCGA and TCGASpliceSeq databases, gene expression and the AS data of UCEC samples were retrieved. These ﬁndings indicate that HSPB1, a splicing factor, regulates the expression of ANKHD1-BP3 to promote metastasis in UCEC. ANKHD1-BP3 may be used as a prognostic biomarker in UCEC.

Practical Implications

Prognostic Biomarker

ANKHD1-BP3 may serve as a prognostic biomarker for UCEC.

Therapeutic Target

Targeting HSPB1 and ANKHD1-BP3 interaction may offer a therapeutic strategy for UCEC metastasis.

Personalized Medicine

Understanding the SFs and ASEs network can pave the way for personalized treatment strategies.

Study Limitations

1
The restricted size of our data and selection bias are the limitations of our analysis
2
we only enriched related pathways from differential genes of RNAseq and only veriﬁed the relationship between UCEC in the PI3K/AKT pathway and apoptosis by WB, which was a superﬁcial exploration at the level of mechanism.
3
only ANKHD1 was accessible. Thus, IHC and WB were used for validation.

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