MYH10 Combines with MYH9 to Recruit USP45 by Deubiquitinating Snail and Promotes Serous Ovarian Cancer Carcinogenesis, Progression, and Cisplatin Resistance
Abstract The poor prognosis of serous ovarian cancer (SOC) is due to its high invasive capacity and cisplatin resistance of SOC cells, whereas the molecular mechanisms remain poorly understood. In the present study, the expression and function of non‐muscle myosin heavy chain IIB (MYH10) in SOC are...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-05-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202203423 |
| _version_ | 1827946006810984448 |
|---|---|
| author | Longyang Liu Chunlin Chen Ping Liu Jing Li Zhanjun Pang Jiayu Zhu Zhongqiu Lin Haixu Zhou Yingying Xie Tiancai Lan Zhe‐Sheng Chen Zhaoyang Zeng Weiyi Fang |
| author_facet | Longyang Liu Chunlin Chen Ping Liu Jing Li Zhanjun Pang Jiayu Zhu Zhongqiu Lin Haixu Zhou Yingying Xie Tiancai Lan Zhe‐Sheng Chen Zhaoyang Zeng Weiyi Fang |
| author_sort | Longyang Liu |
| collection | DOAJ |
| description | Abstract The poor prognosis of serous ovarian cancer (SOC) is due to its high invasive capacity and cisplatin resistance of SOC cells, whereas the molecular mechanisms remain poorly understood. In the present study, the expression and function of non‐muscle myosin heavy chain IIB (MYH10) in SOC are identified by immunohistochemistry, in vitro, and in vivo studies, respectively. The mechanism of MYH10 is demonstrated by co‐immunoprecipitation, GST pull‐down, confocal laser assays, and so on. The results show that the knockdown of MYH10 suppressed SOC cell proliferation, migration, invasion, metastasis, and cisplatin resistance both in vivo and in vitro. Further studies confirm that the MYH10 protein functional domain combines with non‐muscle myosin heavy chain IIA (MYH9) to recruit the deubiquitinating enzyme Ubiquitin‐specific proteases 45 and deubiquitinates snail to inhibit snail degradation, eventually promoting tumorigenesis, progression, and cisplatin resistance in SOC. In clinical samples, MYH10 expression is significantly elevated in SOC samples compared to the paratumor samples. And the expression of MYH10 is positively correlated with MYH9 expression. MYH10+/MYH9+ co‐expression is an independent prognostic factor for predicting SOC patient survival. These findings uncover a key role of the MYH10‐MYH9‐snail axis in SOC carcinogenesis, progression, and cisplatin resistance, and provide potential novel therapeutic targets for SOC intervention. |
| first_indexed | 2024-03-13T10:51:29Z |
| format | Article |
| id | doaj.art-aaf9cc9976224d07b7983af316841ac2 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-13T10:51:29Z |
| publishDate | 2023-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-aaf9cc9976224d07b7983af316841ac22023-05-17T13:02:05ZengWileyAdvanced Science2198-38442023-05-011014n/an/a10.1002/advs.202203423MYH10 Combines with MYH9 to Recruit USP45 by Deubiquitinating Snail and Promotes Serous Ovarian Cancer Carcinogenesis, Progression, and Cisplatin ResistanceLongyang Liu0Chunlin Chen1Ping Liu2Jing Li3Zhanjun Pang4Jiayu Zhu5Zhongqiu Lin6Haixu Zhou7Yingying Xie8Tiancai Lan9Zhe‐Sheng Chen10Zhaoyang Zeng11Weiyi Fang12Department of Gynecology and Obstetrics Nanfang Hospital Southern Medical University Guangzhou 510515 ChinaDepartment of Gynecology and Obstetrics Nanfang Hospital Southern Medical University Guangzhou 510515 ChinaDepartment of Gynecology and Obstetrics Nanfang Hospital Southern Medical University Guangzhou 510515 ChinaDepartment of Gynecology and Obstetrics Nanfang Hospital Southern Medical University Guangzhou 510515 ChinaDepartment of Gynecology and Obstetrics Nanfang Hospital Southern Medical University Guangzhou 510515 ChinaDepartment of Gynecology and Obstetrics Nanfang Hospital Southern Medical University Guangzhou 510515 ChinaDepartment of Gynecological Oncology The Memorial Hospital of Sun Yat‐sen University Guangzhou 510000 ChinaDepartment of Neurosurgery Graduate School of Youjiang Medical University for Nationalities Baise Guangxi 533000 ChinaCancer Center Integrated Hospital of Traditional Chinese Medicine Southern Medical University Guangzhou 510315 ChinaDepartment of Neurosurgery Liuzhou City People's Hospital Guangxi 545000 ChinaInstitute for Biotechnology College of Pharmacy and Health Sciences St. John's University NY 11439 USADepartment of Gynecology Integrated Hospital of Traditional Chinese Medicine Southern Medical University Guangzhou 510315 ChinaCancer Center Integrated Hospital of Traditional Chinese Medicine Southern Medical University Guangzhou 510315 ChinaAbstract The poor prognosis of serous ovarian cancer (SOC) is due to its high invasive capacity and cisplatin resistance of SOC cells, whereas the molecular mechanisms remain poorly understood. In the present study, the expression and function of non‐muscle myosin heavy chain IIB (MYH10) in SOC are identified by immunohistochemistry, in vitro, and in vivo studies, respectively. The mechanism of MYH10 is demonstrated by co‐immunoprecipitation, GST pull‐down, confocal laser assays, and so on. The results show that the knockdown of MYH10 suppressed SOC cell proliferation, migration, invasion, metastasis, and cisplatin resistance both in vivo and in vitro. Further studies confirm that the MYH10 protein functional domain combines with non‐muscle myosin heavy chain IIA (MYH9) to recruit the deubiquitinating enzyme Ubiquitin‐specific proteases 45 and deubiquitinates snail to inhibit snail degradation, eventually promoting tumorigenesis, progression, and cisplatin resistance in SOC. In clinical samples, MYH10 expression is significantly elevated in SOC samples compared to the paratumor samples. And the expression of MYH10 is positively correlated with MYH9 expression. MYH10+/MYH9+ co‐expression is an independent prognostic factor for predicting SOC patient survival. These findings uncover a key role of the MYH10‐MYH9‐snail axis in SOC carcinogenesis, progression, and cisplatin resistance, and provide potential novel therapeutic targets for SOC intervention.https://doi.org/10.1002/advs.202203423cisplatin resistanceMYH10MYH9serous ovarian cancersnail |
| spellingShingle | Longyang Liu Chunlin Chen Ping Liu Jing Li Zhanjun Pang Jiayu Zhu Zhongqiu Lin Haixu Zhou Yingying Xie Tiancai Lan Zhe‐Sheng Chen Zhaoyang Zeng Weiyi Fang MYH10 Combines with MYH9 to Recruit USP45 by Deubiquitinating Snail and Promotes Serous Ovarian Cancer Carcinogenesis, Progression, and Cisplatin Resistance Advanced Science cisplatin resistance MYH10 MYH9 serous ovarian cancer snail |
| title | MYH10 Combines with MYH9 to Recruit USP45 by Deubiquitinating Snail and Promotes Serous Ovarian Cancer Carcinogenesis, Progression, and Cisplatin Resistance |
| title_full | MYH10 Combines with MYH9 to Recruit USP45 by Deubiquitinating Snail and Promotes Serous Ovarian Cancer Carcinogenesis, Progression, and Cisplatin Resistance |
| title_fullStr | MYH10 Combines with MYH9 to Recruit USP45 by Deubiquitinating Snail and Promotes Serous Ovarian Cancer Carcinogenesis, Progression, and Cisplatin Resistance |
| title_full_unstemmed | MYH10 Combines with MYH9 to Recruit USP45 by Deubiquitinating Snail and Promotes Serous Ovarian Cancer Carcinogenesis, Progression, and Cisplatin Resistance |
| title_short | MYH10 Combines with MYH9 to Recruit USP45 by Deubiquitinating Snail and Promotes Serous Ovarian Cancer Carcinogenesis, Progression, and Cisplatin Resistance |
| title_sort | myh10 combines with myh9 to recruit usp45 by deubiquitinating snail and promotes serous ovarian cancer carcinogenesis progression and cisplatin resistance |
| topic | cisplatin resistance MYH10 MYH9 serous ovarian cancer snail |
| url | https://doi.org/10.1002/advs.202203423 |
| work_keys_str_mv | AT longyangliu myh10combineswithmyh9torecruitusp45bydeubiquitinatingsnailandpromotesserousovariancancercarcinogenesisprogressionandcisplatinresistance AT chunlinchen myh10combineswithmyh9torecruitusp45bydeubiquitinatingsnailandpromotesserousovariancancercarcinogenesisprogressionandcisplatinresistance AT pingliu myh10combineswithmyh9torecruitusp45bydeubiquitinatingsnailandpromotesserousovariancancercarcinogenesisprogressionandcisplatinresistance AT jingli myh10combineswithmyh9torecruitusp45bydeubiquitinatingsnailandpromotesserousovariancancercarcinogenesisprogressionandcisplatinresistance AT zhanjunpang myh10combineswithmyh9torecruitusp45bydeubiquitinatingsnailandpromotesserousovariancancercarcinogenesisprogressionandcisplatinresistance AT jiayuzhu myh10combineswithmyh9torecruitusp45bydeubiquitinatingsnailandpromotesserousovariancancercarcinogenesisprogressionandcisplatinresistance AT zhongqiulin myh10combineswithmyh9torecruitusp45bydeubiquitinatingsnailandpromotesserousovariancancercarcinogenesisprogressionandcisplatinresistance AT haixuzhou myh10combineswithmyh9torecruitusp45bydeubiquitinatingsnailandpromotesserousovariancancercarcinogenesisprogressionandcisplatinresistance AT yingyingxie myh10combineswithmyh9torecruitusp45bydeubiquitinatingsnailandpromotesserousovariancancercarcinogenesisprogressionandcisplatinresistance AT tiancailan myh10combineswithmyh9torecruitusp45bydeubiquitinatingsnailandpromotesserousovariancancercarcinogenesisprogressionandcisplatinresistance AT zheshengchen myh10combineswithmyh9torecruitusp45bydeubiquitinatingsnailandpromotesserousovariancancercarcinogenesisprogressionandcisplatinresistance AT zhaoyangzeng myh10combineswithmyh9torecruitusp45bydeubiquitinatingsnailandpromotesserousovariancancercarcinogenesisprogressionandcisplatinresistance AT weiyifang myh10combineswithmyh9torecruitusp45bydeubiquitinatingsnailandpromotesserousovariancancercarcinogenesisprogressionandcisplatinresistance |