Inhibition of EZH2 exerts antitumorigenic effects in renal cell carcinoma via LATS1
The most common type of kidney cancer in adults is renal cell carcinoma (RCC), which accounts for approximately 90% of cases. RCC is a variant disease with numerous subtypes; the most common subtype is clear cell RCC (ccRCC, 75%), followed by papillary RCC (pRCC, 10%) and chromophobe RCC (chRCC, 5%)...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-04-01
|
| Series: | FEBS Open Bio |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/2211-5463.13579 |
| _version_ | 1827974230892871680 |
|---|---|
| author | Seong Hwi Hong Hyun Ji Hwang Da Hyeon Son Eun Song Kim Sung Yul Park Young Eun Yoon |
| author_facet | Seong Hwi Hong Hyun Ji Hwang Da Hyeon Son Eun Song Kim Sung Yul Park Young Eun Yoon |
| author_sort | Seong Hwi Hong |
| collection | DOAJ |
| description | The most common type of kidney cancer in adults is renal cell carcinoma (RCC), which accounts for approximately 90% of cases. RCC is a variant disease with numerous subtypes; the most common subtype is clear cell RCC (ccRCC, 75%), followed by papillary RCC (pRCC, 10%) and chromophobe RCC (chRCC, 5%). To identify a genetic target for all subtypes, we analyzed The Cancer Genome Atlas (TCGA) databases of ccRCC, pRCC, and chromophobe RCC. Enhancer of zeste homolog 2 (EZH2), which encodes a methyltransferase, was observed to be significantly upregulated in tumors. The EZH2 inhibitor tazemetostat induced anticancer effects in RCC cells. TCGA analysis revealed that large tumor suppressor kinase 1 (LATS1), a key tumor suppressor of the Hippo pathway, was significantly downregulated in tumors; the expression of LATS1 was increased by tazemetostat. Through additional experiments, we confirmed that LATS1 plays a crucial role in EZH2 inhibition and has a negative association with EZH2. Therefore, we suggest that epigenetic control could be a novel therapeutic strategy for three subtypes of RCC. |
| first_indexed | 2024-04-09T19:51:01Z |
| format | Article |
| id | doaj.art-8cd5cebba9584020bd81a8426795fbba |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-04-09T19:51:01Z |
| publishDate | 2023-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-8cd5cebba9584020bd81a8426795fbba2023-04-03T06:52:58ZengWileyFEBS Open Bio2211-54632023-04-0113472473510.1002/2211-5463.13579Inhibition of EZH2 exerts antitumorigenic effects in renal cell carcinoma via LATS1Seong Hwi Hong0Hyun Ji Hwang1Da Hyeon Son2Eun Song Kim3Sung Yul Park4Young Eun Yoon5Department of Urology Hanyang University College of Medicine Seoul KoreaDepartment of Urology Hanyang University College of Medicine Seoul KoreaDepartment of Urology Hanyang University College of Medicine Seoul KoreaDepartment of Urology Hanyang University College of Medicine Seoul KoreaDepartment of Urology Hanyang University College of Medicine Seoul KoreaDepartment of Urology Hanyang University College of Medicine Seoul KoreaThe most common type of kidney cancer in adults is renal cell carcinoma (RCC), which accounts for approximately 90% of cases. RCC is a variant disease with numerous subtypes; the most common subtype is clear cell RCC (ccRCC, 75%), followed by papillary RCC (pRCC, 10%) and chromophobe RCC (chRCC, 5%). To identify a genetic target for all subtypes, we analyzed The Cancer Genome Atlas (TCGA) databases of ccRCC, pRCC, and chromophobe RCC. Enhancer of zeste homolog 2 (EZH2), which encodes a methyltransferase, was observed to be significantly upregulated in tumors. The EZH2 inhibitor tazemetostat induced anticancer effects in RCC cells. TCGA analysis revealed that large tumor suppressor kinase 1 (LATS1), a key tumor suppressor of the Hippo pathway, was significantly downregulated in tumors; the expression of LATS1 was increased by tazemetostat. Through additional experiments, we confirmed that LATS1 plays a crucial role in EZH2 inhibition and has a negative association with EZH2. Therefore, we suggest that epigenetic control could be a novel therapeutic strategy for three subtypes of RCC.https://doi.org/10.1002/2211-5463.13579EZH2Hippo pathwayLATS1renal cell carcinomatazemetostat |
| spellingShingle | Seong Hwi Hong Hyun Ji Hwang Da Hyeon Son Eun Song Kim Sung Yul Park Young Eun Yoon Inhibition of EZH2 exerts antitumorigenic effects in renal cell carcinoma via LATS1 FEBS Open Bio EZH2 Hippo pathway LATS1 renal cell carcinoma tazemetostat |
| title | Inhibition of EZH2 exerts antitumorigenic effects in renal cell carcinoma via LATS1 |
| title_full | Inhibition of EZH2 exerts antitumorigenic effects in renal cell carcinoma via LATS1 |
| title_fullStr | Inhibition of EZH2 exerts antitumorigenic effects in renal cell carcinoma via LATS1 |
| title_full_unstemmed | Inhibition of EZH2 exerts antitumorigenic effects in renal cell carcinoma via LATS1 |
| title_short | Inhibition of EZH2 exerts antitumorigenic effects in renal cell carcinoma via LATS1 |
| title_sort | inhibition of ezh2 exerts antitumorigenic effects in renal cell carcinoma via lats1 |
| topic | EZH2 Hippo pathway LATS1 renal cell carcinoma tazemetostat |
| url | https://doi.org/10.1002/2211-5463.13579 |
| work_keys_str_mv | AT seonghwihong inhibitionofezh2exertsantitumorigeniceffectsinrenalcellcarcinomavialats1 AT hyunjihwang inhibitionofezh2exertsantitumorigeniceffectsinrenalcellcarcinomavialats1 AT dahyeonson inhibitionofezh2exertsantitumorigeniceffectsinrenalcellcarcinomavialats1 AT eunsongkim inhibitionofezh2exertsantitumorigeniceffectsinrenalcellcarcinomavialats1 AT sungyulpark inhibitionofezh2exertsantitumorigeniceffectsinrenalcellcarcinomavialats1 AT youngeunyoon inhibitionofezh2exertsantitumorigeniceffectsinrenalcellcarcinomavialats1 |