Single-cell analysis of AIMP2 splice variants informs on drug sensitivity and prognosis in hematologic cancer

Jayoung Ku; Ryul Kim; Dongchan Kim; Daeyoon Kim; Seulki Song; Keonyong Lee; Namseok Lee; Min A. Kim; Sung Soo Yoon; Nam Hoon Kwon; Sunghoon Kim; Yoosik Kim; Youngil Koh

doi:10.1038/s42003-020-01353-x

Single-cell analysis of AIMP2 splice variants informs on drug sensitivity and prognosis in hematologic cancer

Jayoung Ku, Ryul Kim, Dongchan Kim, Daeyoon Kim, Seulki Song, Keonyong Lee, Namseok Lee, Min A. Kim, Sung Soo Yoon, Nam Hoon Kwon, Sunghoon Kim, Yoosik Kim, Youngil Koh

Department of Pharmacy

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

Aminoacyl-tRNA synthetase-interacting multifunctional protein 2 (AIMP2) is a non-enzymatic component required for the multi-tRNA synthetase complex. While exon 2 skipping alternatively spliced variant of AIMP2 (AIMP2-DX2) compromises AIMP2 activity and is associated with carcinogenesis, its clinical potential awaits further validation. Here, we found that AIMP2-DX2/AIMP2 expression ratio is strongly correlated with major cancer signaling pathways and poor prognosis, particularly in acute myeloid leukemia (AML). Analysis of a clinical patient cohort revealed that AIMP2-DX2 positive AML patients show decreased overall survival and progression-free survival. We also developed targeted RNA-sequencing and single-molecule RNA-FISH tools to quantitatively analyze AIMP2-DX2/AIMP2 ratios at the single-cell level. By subclassifying hematologic cancer cells based on their AIMP2-DX2/AIMP2 ratios, we found that downregulating AIMP2-DX2 sensitizes cells to anticancer drugs only for a subgroup of cells while it has adverse effects on others. Collectively, our study establishes AIMP2-DX2 as a potential biomarker and a therapeutic target for hematologic cancer.

Original language	English
Article number	630
Journal	Communications Biology
Volume	3
Issue number	1
DOIs	https://doi.org/10.1038/s42003-020-01353-x
Publication status	Published - 2020 Dec 1

Bibliographical note

Funding Information:
This work was funded by the Korean government Ministry of Science, ICT & Future Planning (NRF-2019R1C1C1006672) and National Research Foundation (NRF) grant for Basic Research Lab (No. NRF-2018R1A4A1022513) funded by the Korean government (MSIP, Ministry of Science, ICT& Future Planning). This research was also supported with the computing resources by Global Science experimental Data hub Center (GSDC) & Korea Research Environment Open NETwork (KREONET).

Publisher Copyright:
© 2020, The Author(s).

All Science Journal Classification (ASJC) codes

Medicine (miscellaneous)
Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s42003-020-01353-x

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title = "Single-cell analysis of AIMP2 splice variants informs on drug sensitivity and prognosis in hematologic cancer",

abstract = "Aminoacyl-tRNA synthetase-interacting multifunctional protein 2 (AIMP2) is a non-enzymatic component required for the multi-tRNA synthetase complex. While exon 2 skipping alternatively spliced variant of AIMP2 (AIMP2-DX2) compromises AIMP2 activity and is associated with carcinogenesis, its clinical potential awaits further validation. Here, we found that AIMP2-DX2/AIMP2 expression ratio is strongly correlated with major cancer signaling pathways and poor prognosis, particularly in acute myeloid leukemia (AML). Analysis of a clinical patient cohort revealed that AIMP2-DX2 positive AML patients show decreased overall survival and progression-free survival. We also developed targeted RNA-sequencing and single-molecule RNA-FISH tools to quantitatively analyze AIMP2-DX2/AIMP2 ratios at the single-cell level. By subclassifying hematologic cancer cells based on their AIMP2-DX2/AIMP2 ratios, we found that downregulating AIMP2-DX2 sensitizes cells to anticancer drugs only for a subgroup of cells while it has adverse effects on others. Collectively, our study establishes AIMP2-DX2 as a potential biomarker and a therapeutic target for hematologic cancer.",

author = "Jayoung Ku and Ryul Kim and Dongchan Kim and Daeyoon Kim and Seulki Song and Keonyong Lee and Namseok Lee and Kim, {Min A.} and Yoon, {Sung Soo} and Kwon, {Nam Hoon} and Sunghoon Kim and Yoosik Kim and Youngil Koh",

note = "Funding Information: This work was funded by the Korean government Ministry of Science, ICT & Future Planning (NRF-2019R1C1C1006672) and National Research Foundation (NRF) grant for Basic Research Lab (No. NRF-2018R1A4A1022513) funded by the Korean government (MSIP, Ministry of Science, ICT& Future Planning). This research was also supported with the computing resources by Global Science experimental Data hub Center (GSDC) & Korea Research Environment Open NETwork (KREONET). Publisher Copyright: {\textcopyright} 2020, The Author(s).",

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AU - Kim, Ryul

AU - Kim, Dongchan

AU - Kim, Daeyoon

AU - Song, Seulki

AU - Lee, Keonyong

AU - Lee, Namseok

AU - Kim, Min A.

AU - Yoon, Sung Soo

AU - Kwon, Nam Hoon

AU - Kim, Sunghoon

AU - Kim, Yoosik

AU - Koh, Youngil

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PY - 2020/12/1

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N2 - Aminoacyl-tRNA synthetase-interacting multifunctional protein 2 (AIMP2) is a non-enzymatic component required for the multi-tRNA synthetase complex. While exon 2 skipping alternatively spliced variant of AIMP2 (AIMP2-DX2) compromises AIMP2 activity and is associated with carcinogenesis, its clinical potential awaits further validation. Here, we found that AIMP2-DX2/AIMP2 expression ratio is strongly correlated with major cancer signaling pathways and poor prognosis, particularly in acute myeloid leukemia (AML). Analysis of a clinical patient cohort revealed that AIMP2-DX2 positive AML patients show decreased overall survival and progression-free survival. We also developed targeted RNA-sequencing and single-molecule RNA-FISH tools to quantitatively analyze AIMP2-DX2/AIMP2 ratios at the single-cell level. By subclassifying hematologic cancer cells based on their AIMP2-DX2/AIMP2 ratios, we found that downregulating AIMP2-DX2 sensitizes cells to anticancer drugs only for a subgroup of cells while it has adverse effects on others. Collectively, our study establishes AIMP2-DX2 as a potential biomarker and a therapeutic target for hematologic cancer.

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Single-cell analysis of AIMP2 splice variants informs on drug sensitivity and prognosis in hematologic cancer

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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