ALKBH1 contributes to renal cell carcinoma progression by reducing N6-methyladenine of GPR137
© 2023 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd..
BACKGROUND: Renal cell carcinoma (RCC) accounts for approximately 4% of all adult malignancies with high mortality worldwide. Although conventional chemotherapy and radiotherapy treatment has been applied for RCC in clinic, the mortality rate of patients is increasing each year, and patients with metastatic RCC are still suffering from poor prognosis. Thus, further investigation of the molecular mechanisms responsible for the development and progression of RCC is of particular importance.
METHODS: Total of 10 pairs of RCC tissues and adjacent nontumor tissues were collected for examination of ALKBH1 and GPR137 expression. The correlations between ALKBH1 and GPR137 expression in RCC patient were assessed by GEPIA online tool and were analyzed using auto best cutoff. The human RCC cell lines Caki-1, 786-O, ACHN, Osrc2, A498, and 769-P, were used for mechanistic investigation.
RESULTS: Here, we report that the expression of AlkB homologue 1 (ALKBH1) is upregulated in RCC tissues, which is correlated with G-protein-coupled receptor 137 (GPR137) expression. The elevated expression of ALKBH1 is associated with RCC cell malignant characteristics, including cell proliferation and movement (migration and invasion). Mechanistic investigation further reveals that ALKBH1 reduces m6 A levels of GPR137 mRNA in RCC cells, which upregulates GPR137 mRNA levels, resulting in the increased GPR137 protein expression subsequently and the enhanced RCC cell biological actions consequently. In contrast, the suppression of GPR137 effectively alleviates the ALKBH1-induced malignancies of RCC cells.
CONCLUSION: Our results indicate that ALKBH1-GPR137 axis might be used as a potential therapeutic target in RCC, contributing to finding new prognostic biomarkers for RCC at an early stage.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:53 |
|---|---|
| Enthalten in: |
European journal of clinical investigation - 53(2023), 7 vom: 27. Juli, Seite e13986 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Li, Lin [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
ALKBH1 |
|---|
| Anmerkungen: |
Date Completed 13.06.2023 Date Revised 13.06.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1111/eci.13986 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM354258788 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM354258788 | ||
| 003 | DE-627 | ||
| 005 | 20231226061828.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/eci.13986 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1180.xml |
| 035 | |a (DE-627)NLM354258788 | ||
| 035 | |a (NLM)36920340 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Li, Lin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a ALKBH1 contributes to renal cell carcinoma progression by reducing N6-methyladenine of GPR137 |
| 264 | 1 | |c 2023 | |
| 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 Completed 13.06.2023 | ||
| 500 | |a Date Revised 13.06.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd. | ||
| 520 | |a BACKGROUND: Renal cell carcinoma (RCC) accounts for approximately 4% of all adult malignancies with high mortality worldwide. Although conventional chemotherapy and radiotherapy treatment has been applied for RCC in clinic, the mortality rate of patients is increasing each year, and patients with metastatic RCC are still suffering from poor prognosis. Thus, further investigation of the molecular mechanisms responsible for the development and progression of RCC is of particular importance | ||
| 520 | |a METHODS: Total of 10 pairs of RCC tissues and adjacent nontumor tissues were collected for examination of ALKBH1 and GPR137 expression. The correlations between ALKBH1 and GPR137 expression in RCC patient were assessed by GEPIA online tool and were analyzed using auto best cutoff. The human RCC cell lines Caki-1, 786-O, ACHN, Osrc2, A498, and 769-P, were used for mechanistic investigation | ||
| 520 | |a RESULTS: Here, we report that the expression of AlkB homologue 1 (ALKBH1) is upregulated in RCC tissues, which is correlated with G-protein-coupled receptor 137 (GPR137) expression. The elevated expression of ALKBH1 is associated with RCC cell malignant characteristics, including cell proliferation and movement (migration and invasion). Mechanistic investigation further reveals that ALKBH1 reduces m6 A levels of GPR137 mRNA in RCC cells, which upregulates GPR137 mRNA levels, resulting in the increased GPR137 protein expression subsequently and the enhanced RCC cell biological actions consequently. In contrast, the suppression of GPR137 effectively alleviates the ALKBH1-induced malignancies of RCC cells | ||
| 520 | |a CONCLUSION: Our results indicate that ALKBH1-GPR137 axis might be used as a potential therapeutic target in RCC, contributing to finding new prognostic biomarkers for RCC at an early stage | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ALKBH1 | |
| 650 | 4 | |a GPR137 | |
| 650 | 4 | |a m6A | |
| 650 | 4 | |a malignancy | |
| 650 | 4 | |a renal cell carcinoma | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a ALKBH1 protein, human |2 NLM | |
| 650 | 7 | |a EC 1.14.11.33 |2 NLM | |
| 650 | 7 | |a AlkB Homolog 1, Histone H2a Dioxygenase |2 NLM | |
| 650 | 7 | |a EC 1.14.11.33 |2 NLM | |
| 700 | 1 | |a Zhu, Chongying |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Shouying |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Jianqing |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Da |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Gan, Sishun |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Bing |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Chao |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t European journal of clinical investigation |d 1970 |g 53(2023), 7 vom: 27. Juli, Seite e13986 |w (DE-627)NLM000003107 |x 1365-2362 |7 nnns |
| 773 | 1 | 8 | |g volume:53 |g year:2023 |g number:7 |g day:27 |g month:07 |g pages:e13986 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1111/eci.13986 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 53 |j 2023 |e 7 |b 27 |c 07 |h e13986 | ||