The m6A regulator KIAA1429 stabilizes RAB27B mRNA and promotes the progression of chronic myeloid leukemia and resistance to targeted therapy
© 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd..
Chronic myeloid leukemia (CML) is a common adult leukemia. Both the acute phase of the disease and the adverse effects of anti-cancer treatments can lead to a poor prognosis. The N6-methyladenine (m6A) modification plays an important regulatory role in various physiological and pathological processes. KIAA1429 is a known m6A regulator, but the biological role of KIAA1429 in CML is unclear. In this study, we observed that the m6A levels and KIAA1429 expression were significantly up-regulated in patients with blast phase CML. Notably, KIAA1429 regulated the total level of RNA m6A modification in the CML cells and promoted the malignant biological behaviors of CML cells, including proliferation, migration, and imatinib resistance. Inhibiting KIAA1429 in CML cells reduced the stability of RAB27B mRNA through the m6A/YTHDF1 axis, consequently inhibiting CML proliferation and drug efflux, ultimately increasing the sensitivity of CML cells to imatinib. Moreover, the knockdown of RAB27B also inhibited the proliferation and drug resistance of CML cells and promoted their apoptosis. Rucaparib, a recently developed anti-cancer agent, suppressed the expression of KIAA1429 and CML cell proliferation and promoted cell apoptosis. Rucaparib also inhibited the tumorigenesis of CML cells in vivo. The combined use of rucaparib and imatinib enhanced the sensitivity of CML cells to imatinib. Our study provides evidence that elevated KIAA1429 expression in the blast phase of CML enhances the stability of RAB27B mRNA through the m6A/YTHDF1 axis to up-regulate RAB27B expression, thereby promoting CML progression. Rucaparib exerts inhibitory effects on KIAA1429 expression and thus reduces CML progression.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 2023 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
|---|---|
| Enthalten in: |
Genes & diseases - 11(2023), 2 vom: 19. März, Seite 993-1008 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Yao, Fangyi [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Chronic myeloid leukemia |
|---|
| Anmerkungen: |
Date Revised 13.09.2023 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.1016/j.gendis.2023.03.016 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM361899521 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM361899521 | ||
| 003 | DE-627 | ||
| 005 | 20231226090124.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.gendis.2023.03.016 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1206.xml |
| 035 | |a (DE-627)NLM361899521 | ||
| 035 | |a (NLM)37692484 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Yao, Fangyi |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The m6A regulator KIAA1429 stabilizes RAB27B mRNA and promotes the progression of chronic myeloid leukemia and resistance to targeted therapy |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 13.09.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. | ||
| 520 | |a Chronic myeloid leukemia (CML) is a common adult leukemia. Both the acute phase of the disease and the adverse effects of anti-cancer treatments can lead to a poor prognosis. The N6-methyladenine (m6A) modification plays an important regulatory role in various physiological and pathological processes. KIAA1429 is a known m6A regulator, but the biological role of KIAA1429 in CML is unclear. In this study, we observed that the m6A levels and KIAA1429 expression were significantly up-regulated in patients with blast phase CML. Notably, KIAA1429 regulated the total level of RNA m6A modification in the CML cells and promoted the malignant biological behaviors of CML cells, including proliferation, migration, and imatinib resistance. Inhibiting KIAA1429 in CML cells reduced the stability of RAB27B mRNA through the m6A/YTHDF1 axis, consequently inhibiting CML proliferation and drug efflux, ultimately increasing the sensitivity of CML cells to imatinib. Moreover, the knockdown of RAB27B also inhibited the proliferation and drug resistance of CML cells and promoted their apoptosis. Rucaparib, a recently developed anti-cancer agent, suppressed the expression of KIAA1429 and CML cell proliferation and promoted cell apoptosis. Rucaparib also inhibited the tumorigenesis of CML cells in vivo. The combined use of rucaparib and imatinib enhanced the sensitivity of CML cells to imatinib. Our study provides evidence that elevated KIAA1429 expression in the blast phase of CML enhances the stability of RAB27B mRNA through the m6A/YTHDF1 axis to up-regulate RAB27B expression, thereby promoting CML progression. Rucaparib exerts inhibitory effects on KIAA1429 expression and thus reduces CML progression | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Chronic myeloid leukemia | |
| 650 | 4 | |a KIAA1429 | |
| 650 | 4 | |a N6-methyladenine | |
| 650 | 4 | |a RAB27B | |
| 650 | 4 | |a Rucaparib | |
| 650 | 4 | |a YTHDF1 | |
| 700 | 1 | |a Zhong, Fangmin |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Junyao |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Shuai |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Shuqi |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Meiyong |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Yanmei |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiaozhong |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Genes & diseases |d 2014 |g 11(2023), 2 vom: 19. März, Seite 993-1008 |w (DE-627)NLM242912818 |x 2352-3042 |7 nnns |
| 773 | 1 | 8 | |g volume:11 |g year:2023 |g number:2 |g day:19 |g month:03 |g pages:993-1008 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.gendis.2023.03.016 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 11 |j 2023 |e 2 |b 19 |c 03 |h 993-1008 | ||