lncRNA HOTTIP Recruits EZH2 to Inhibit PTEN Expression and Participates in IM Resistance in Chronic Myeloid Leukemia

Objective. To investigate that HOTTIP suppressed PTEN gene expression and was involved in IM resistance in chronic myeloid leukemia through recruitment of EZH2 protein. Methods. Seventy-one cases of bone marrow monocytes diagnosed with CML in the Second Hospital of Hebei Medical University from 2018...

Full description

Saved in:
Bibliographic Details
Main Authors: Jing Liu, Lin Yang, Xiaojun Liu, Lu Liu, Menghan Liu, Xuefeng Feng, Jianmin Luo
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2022/9993393
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832562307394174976
author Jing Liu
Lin Yang
Xiaojun Liu
Lu Liu
Menghan Liu
Xuefeng Feng
Jianmin Luo
author_facet Jing Liu
Lin Yang
Xiaojun Liu
Lu Liu
Menghan Liu
Xuefeng Feng
Jianmin Luo
author_sort Jing Liu
collection DOAJ
description Objective. To investigate that HOTTIP suppressed PTEN gene expression and was involved in IM resistance in chronic myeloid leukemia through recruitment of EZH2 protein. Methods. Seventy-one cases of bone marrow monocytes diagnosed with CML in the Second Hospital of Hebei Medical University from 2018 to 2021 were selected. These patients were diagnosed with CML by bone marrow morphology, immunology, molecular biology, and cytogenetics, of which 36 were sensitive to IM and 35 were resistant to IM. We selected K562 and IR-K562 cells preserved in the laboratory as our subjects to study the expression levels of HOTTIP in the bone marrow cells of IM CML-resistant patients and IM-resistant cells. Results. In this study, we found that HOTTIP was highly expressed in the bone marrow and cell lines of CML patients resistant to Imatinib mesylate (IM). In in vitro experiments, lentiviral knockdown of HOTTIP inhibited CML cell proliferation and promoted apoptosis, and knockdown of HOTTIP also increased sensitivity to IM. Mechanistically, highly expressed HOTTIP is involved in the biological process of IM resistance by recruiting Zeste homologous protein 2 enhancer (EZH2) to inhibit the expression of phosphatase and Tensin homologous protein (PTEN) genes. Conclusions. We confirmed that HOTTIP and EZH2 are highly expressed in IM-resistant patients and IM-resistant CML cell lines. In CML cell lines, HOTTIP is involved in regulating the proliferation and apoptosis of CML cells and resistance to IM.
format Article
id doaj-art-19c58a893abf484183483666fcfd007b
institution Kabale University
issn 1687-9678
language English
publishDate 2022-01-01
publisher Wiley
record_format Article
series Stem Cells International
spelling doaj-art-19c58a893abf484183483666fcfd007b2025-02-03T01:22:56ZengWileyStem Cells International1687-96782022-01-01202210.1155/2022/9993393lncRNA HOTTIP Recruits EZH2 to Inhibit PTEN Expression and Participates in IM Resistance in Chronic Myeloid LeukemiaJing Liu0Lin Yang1Xiaojun Liu2Lu Liu3Menghan Liu4Xuefeng Feng5Jianmin Luo6Key Laboratory of HematologyKey Laboratory of HematologyKey Laboratory of HematologyKey Laboratory of HematologyKey Laboratory of HematologyKey Laboratory of HematologyKey Laboratory of HematologyObjective. To investigate that HOTTIP suppressed PTEN gene expression and was involved in IM resistance in chronic myeloid leukemia through recruitment of EZH2 protein. Methods. Seventy-one cases of bone marrow monocytes diagnosed with CML in the Second Hospital of Hebei Medical University from 2018 to 2021 were selected. These patients were diagnosed with CML by bone marrow morphology, immunology, molecular biology, and cytogenetics, of which 36 were sensitive to IM and 35 were resistant to IM. We selected K562 and IR-K562 cells preserved in the laboratory as our subjects to study the expression levels of HOTTIP in the bone marrow cells of IM CML-resistant patients and IM-resistant cells. Results. In this study, we found that HOTTIP was highly expressed in the bone marrow and cell lines of CML patients resistant to Imatinib mesylate (IM). In in vitro experiments, lentiviral knockdown of HOTTIP inhibited CML cell proliferation and promoted apoptosis, and knockdown of HOTTIP also increased sensitivity to IM. Mechanistically, highly expressed HOTTIP is involved in the biological process of IM resistance by recruiting Zeste homologous protein 2 enhancer (EZH2) to inhibit the expression of phosphatase and Tensin homologous protein (PTEN) genes. Conclusions. We confirmed that HOTTIP and EZH2 are highly expressed in IM-resistant patients and IM-resistant CML cell lines. In CML cell lines, HOTTIP is involved in regulating the proliferation and apoptosis of CML cells and resistance to IM.http://dx.doi.org/10.1155/2022/9993393
spellingShingle Jing Liu
Lin Yang
Xiaojun Liu
Lu Liu
Menghan Liu
Xuefeng Feng
Jianmin Luo
lncRNA HOTTIP Recruits EZH2 to Inhibit PTEN Expression and Participates in IM Resistance in Chronic Myeloid Leukemia
Stem Cells International
title lncRNA HOTTIP Recruits EZH2 to Inhibit PTEN Expression and Participates in IM Resistance in Chronic Myeloid Leukemia
title_full lncRNA HOTTIP Recruits EZH2 to Inhibit PTEN Expression and Participates in IM Resistance in Chronic Myeloid Leukemia
title_fullStr lncRNA HOTTIP Recruits EZH2 to Inhibit PTEN Expression and Participates in IM Resistance in Chronic Myeloid Leukemia
title_full_unstemmed lncRNA HOTTIP Recruits EZH2 to Inhibit PTEN Expression and Participates in IM Resistance in Chronic Myeloid Leukemia
title_short lncRNA HOTTIP Recruits EZH2 to Inhibit PTEN Expression and Participates in IM Resistance in Chronic Myeloid Leukemia
title_sort lncrna hottip recruits ezh2 to inhibit pten expression and participates in im resistance in chronic myeloid leukemia
url http://dx.doi.org/10.1155/2022/9993393
work_keys_str_mv AT jingliu lncrnahottiprecruitsezh2toinhibitptenexpressionandparticipatesinimresistanceinchronicmyeloidleukemia
AT linyang lncrnahottiprecruitsezh2toinhibitptenexpressionandparticipatesinimresistanceinchronicmyeloidleukemia
AT xiaojunliu lncrnahottiprecruitsezh2toinhibitptenexpressionandparticipatesinimresistanceinchronicmyeloidleukemia
AT luliu lncrnahottiprecruitsezh2toinhibitptenexpressionandparticipatesinimresistanceinchronicmyeloidleukemia
AT menghanliu lncrnahottiprecruitsezh2toinhibitptenexpressionandparticipatesinimresistanceinchronicmyeloidleukemia
AT xuefengfeng lncrnahottiprecruitsezh2toinhibitptenexpressionandparticipatesinimresistanceinchronicmyeloidleukemia
AT jianminluo lncrnahottiprecruitsezh2toinhibitptenexpressionandparticipatesinimresistanceinchronicmyeloidleukemia