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tRF-20-M0NK5Y93-induced MALAT1 promotes colon cancer metastasis through alternative splicing of SMC1A

Na Luan1, Jiaojiao Wang2, Biao Sheng2

  • 1Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, 2nd Affiliated Hospital, Zhejiang University School of Medicine Jiefang Road 88th, Hangzhou, China.

American Journal of Cancer Research
|April 10, 2023
PubMed

Insights

A specific tRNA-derived fragment (tRF) inhibits colon cancer metastasis by regulating alternative splicing of the SMC1A gene. This discovery reveals a novel mechanism involving noncoding RNAs and offers a potential therapeutic target for colon cancer.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Noncoding RNA Biology

Background:

  • Tumor microenvironment changes, like hypoxia, alter noncoding small RNA tRNA-derived fragments (tRFs) expression, impacting tumor metastasis.
  • The precise mechanisms of tRFs in mediating tumor metastasis and their regulatory relationship with long noncoding RNAs (lncRNAs) and alternative splicing remain unclear.

Purpose of the Study:

  • To elucidate the mechanism of tRF-mediated alternative splicing of SMC1A and its role in colon cancer metastasis.
  • To investigate the interactions between tRFs, lncRNAs, and splicing factors in the context of colon cancer.

Main Methods:

  • Multi-dimensional study including cell, molecular, animal, and clinical analyses.
  • Complete transcriptional sequencing and bioinformatics analyses to identify correlations.
  • Mechanistic investigations involving RNA-binding assays and splicing analysis.

Main Results:

  • tRF-20-M0NK5Y93 was identified as an inhibitor of colon cancer metastasis.
  • Significant correlations were found between tRFs, metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), and SRSF2 expression.
  • tRFs regulate MALAT-1 expression, which in turn interacts with SRSF2 to control alternative splicing of SMC1A, leading to varied isoform expression.

Conclusions:

  • A novel regulatory pathway involving tRFs, MALAT-1, and SRSF2 in controlling SMC1A alternative splicing and colon cancer metastasis has been uncovered.
  • The interaction between different noncoding RNAs in regulating alternative splicing presents a potential new therapeutic target for colon cancer.
Keywords:
MALAT1SMC1ASRSF2ncRNAtRFs

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