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 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.

LncRNA BlncAD1 Modulates Bovine Adipogenesis by Binding to MYH10, PI3K/Akt Signaling Pathway, and miR-27a-5p/CDK6 Axis

“…MYH10 was identified as a protein partner of BlncAD1 , and this relationship was supported by the results of RNA pull-down, RIP, and colocalization assays. Previous studies have shown that MYH10 knockdown inhibits the proliferation of SOC cells . It has been reported that MYH10 is a novel regulator of adipogenesis, and knockdown of MYH10 leads to impaired adipogenesis in preadipocytes .…”

“…Previous studies have shown that MYH10 knockdown inhibits the proliferation of SOC cells. 32 It has been reported that MYH10 is a novel regulator of adipogenesis, and knockdown of MYH10 leads to impaired adipogenesis in preadipocytes. 24 Our results revealed that knockdown of MYH10 inhibited the proliferation and differentiation of bovine preadipocytes.…”

Discovery and Validation of Survival-Specific Genes in Papillary Renal Cell Carcinoma Using a Customized Next-Generation Sequencing Gene Panel

“…However, a hepatocellular carcinoma (HCC) research study has reported that genomic depletion at the MYH10 locus (17p13.1) is significantly correlated with decreased OS ( p = 0.017, HR = 1.55) and DFS ( p = 0.003, HR = 1.59) and that the downregulation of MYH10 can promote HCC metastasis [ 68 ]. A serous ovarian cancer research study has reported that MYH10 expression is associated with intraperitoneal metastasis ( p < 0.0001) and intestinal metastasis ( p = 0.0281) [ 69 ].…”

Comprehensive analysis of disulfidptosis related genes and prognosis of gastric cancer

“…It has also been found that the high expression of FLNA can lead to low survival rate and migration and invasion energy of GC cells[ 69 ]. Additionally, the disulfidptosis-related gene MYH10 may be related to the occurrence, development, and drug resistance of ovarian cancer[ 70 ], but its role in GC requires further exploration. Moreover, previous studies have revealed that DSTN increases the colony formation and migration ability of tumor cells when highly expressed[ 71 ], although its relationship with GC prognosis requires further study.…”