Figure 7
HAPSTR1 exerts its oncogenic functions in ovarian cancer through LRPPRC. (A) Protein expression levels of LRPPRC were positively correlated with HAPSTR1 via Western blot. (B) Transfection efficiency of HAPSTR1 and LRPPRC were examined by Western blot. (C-E) The colony formation and transwell assays showed that the suppression of proliferative capacity induced by HAPSTR1 knockdown could be rescued by LRPPRC overexpression. Original magnification, 200x. (F-I) The CCK-8, colony formation, and transwell assays showed that the improvements in proliferative and metastatic capability caused by HAPSTR1 overexpression could be inhibited by LRPPRC knockdown. Original magnification, 200x. Each experiment was repeated with three independent replicates. *, p < 0.05; **, p < 0.01; ***, p < 0.001.
Source publication
Ovarian cancer is the second most common cause of gynecologic cancer death. Chemoresistance and metastasis remain major challenges for current treatment. Previously, HAPSTR1 was shown to be a target gene of a paclitaxel resistance-associated miRNA. However, the biological function and underlying molecular mechanisms of HAPSTR1 in ovarian cancer pro...
Contexts in source publication
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... the regulatory relationship between HAPSTR1 and LRPPRC, we found that HAPSTR1 overexpression led to the upregulation of LRPPRC, whereas HAPSTR1 knockdown exerted the opposite effect ( Figure 7A). LRPPRC was suppressed following HAPSTR1 knockdown. ...
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... was suppressed following HAPSTR1 knockdown. We detected the dual transfection efficiency of HAPSTR1 and LRPPRC ( Figure 7B). These results demonstrate that LRPPRC overexpression alleviated the suppression of proliferation, invasion, and migration induced by silencing HAPSTR1 in SKOV3 cells ( Figure 7C-7E). ...
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... detected the dual transfection efficiency of HAPSTR1 and LRPPRC ( Figure 7B). These results demonstrate that LRPPRC overexpression alleviated the suppression of proliferation, invasion, and migration induced by silencing HAPSTR1 in SKOV3 cells ( Figure 7C-7E). Subsequently, LRPPRC was knocked down while HAPSTR1 was overexpressed; LRPPRC repression inhibited the proliferation, invasion, and migration caused by HAPSTR1 overexpression in A2780 cells ( Figure 7F-7I). ...
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... results demonstrate that LRPPRC overexpression alleviated the suppression of proliferation, invasion, and migration induced by silencing HAPSTR1 in SKOV3 cells ( Figure 7C-7E). Subsequently, LRPPRC was knocked down while HAPSTR1 was overexpressed; LRPPRC repression inhibited the proliferation, invasion, and migration caused by HAPSTR1 overexpression in A2780 cells ( Figure 7F-7I). ...
Citations
... Such observations are in keeping with the correlation between RPN11/PSMD14 and LRPPRC expression in clinical specimens [76]. The C16orf72/HUWE1associated protein modifying stress responses (HAPSTR1) has also been implicated in sustaining tumor progression in ovarian cancer through stimulation of epithelial mesenchymal transition (EMT) and inhibition of autophagy [77]. Indeed, HAPSTR1 colocalizes with LRPPRC and inhibits its ubiquitination, with HAPSTR1 overexpression stabilizing LRPPRC through RPN11/PSMD14. ...
Ovarian cancer is a lethal disease due to late diagnosis and occurrence of drug resistance that limits the efficacy of platinum-based therapy. Drug resistance mechanisms include both tumor intrinsic and tumor microenvironment-related factors. A role for deubiquitinases (DUBs) is starting to emerge in ovarian cancer. DUBs are a large family of enzymes that remove ubiquitin from target proteins and participate in processes affecting drug resistance such as DNA damage repair and apoptosis. Besides, DUBs modulate the functions of T cell populations favoring an immune suppressed microenvironment. Three DUBs are proteasome-associated, whereas the large majority are not. Among the former DUBs, USP14 has been proposed to modulate transcription factors such as Bcl6 and BACH1. In addition, RPN11/PSMD14 interferes with various processes including epithelial mesenchymal transition, also favored by non-proteasomal DUBs such as USP1 by acting on Snail. Besides, USP8 by stabilizing HER family receptors can confer drug resistance. Overall, DUBs appear to be druggable, with several inhibitors under development. Based on DUBs biological role, DUBs targeting appears promising in view of combination strategies involving different therapeutic approaches. Here, we summarize the relevance of DUBs in ovarian carcinoma and provide insights into future challenges for the treatment of this disease.
