Scaffold protein MAPK8IP2 expression is a robust prognostic factor in prostate cancer associated with AR signaling activity
Mitogen-activated protein kinase-8-interacting protein 2 (MAPK8IP2) is a scaffold protein that modulates MAPK signal cascades. Although MAPK pathways were heavily implicated in prostate cancer progression, the regulation of MAPK8IP2 expression in prostate cancer is not yet reported. We assessed MAPK...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2023-01-01
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| Series: | Asian Journal of Andrology |
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| Online Access: | http://www.ajandrology.com/article.asp?issn=1008-682X;year=2023;volume=25;issue=2;spage=198;epage=207;aulast=Huang |
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| author | Jian Huang Wang Liu Bi-Yun Lin Jean C Li Jane Lu Ben-Yi Li |
| author_facet | Jian Huang Wang Liu Bi-Yun Lin Jean C Li Jane Lu Ben-Yi Li |
| author_sort | Jian Huang |
| collection | DOAJ |
| description | Mitogen-activated protein kinase-8-interacting protein 2 (MAPK8IP2) is a scaffold protein that modulates MAPK signal cascades. Although MAPK pathways were heavily implicated in prostate cancer progression, the regulation of MAPK8IP2 expression in prostate cancer is not yet reported. We assessed MAPK8IP2 gene expression in prostate cancer related to disease progression and patient survival outcomes. MAPK8IP2 expression was analyzed using multiple genome-wide gene expression datasets derived from The Cancer Genome Atlas (TCGA) RNA-sequence project and complementary DNA (cDNA) microarrays. Multivariable Cox regressions and log-rank tests were used to analyze the overall survival outcome and progression-free interval. MAPK8IP2 protein expression was evaluated using the immunohistochemistry approach. The quantitative PCR and Western blot methods analyzed androgen-stimulated MAPK8IP2 expression in LNCaP cells. In primary prostate cancer tissues, MAPK8IP2 mRNA expression levels were significantly higher than those in the case-matched benign prostatic tissues. Increased MAPK8IP2 expression was strongly correlated with late tumor stages, lymph node invasion, residual tumors after surgery, higher Gleason scores, and preoperational serum prostate-specific antigen (PSA) levels. MAPK8IP2 upregulation was significantly associated with worse overall survival outcomes and progression-free intervals. In castration-resistant prostate cancers, MAPK8IP2 expression strongly correlated with androgen receptor (AR) signaling activity. In cell culture-based experiments, MAPK8IP2 expression was stimulated by androgens in AR-positive prostate cancer cells. However, MAPK8IP2 expression was blocked by AR antagonists only in androgen-sensitive LNCaP but not castration-resistant C4-2B and 22RV1 cells. These results indicate that MAPK8IP2 is a robust prognostic factor and therapeutic biomarker for prostate cancer. The potential role of MAPK8IP2 in the castration-resistant progression is under further investigation. |
| first_indexed | 2024-04-09T23:30:05Z |
| format | Article |
| id | doaj.art-cc22409beddb4694b88b350e0fa6b12f |
| institution | Directory Open Access Journal |
| issn | 1008-682X 1745-7262 |
| language | English |
| last_indexed | 2024-04-09T23:30:05Z |
| publishDate | 2023-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Asian Journal of Andrology |
| spelling | doaj.art-cc22409beddb4694b88b350e0fa6b12f2023-03-21T07:26:14ZengWolters Kluwer Medknow PublicationsAsian Journal of Andrology1008-682X1745-72622023-01-0125219820710.4103/aja202240Scaffold protein MAPK8IP2 expression is a robust prognostic factor in prostate cancer associated with AR signaling activityJian HuangWang LiuBi-Yun LinJean C LiJane LuBen-Yi LiMitogen-activated protein kinase-8-interacting protein 2 (MAPK8IP2) is a scaffold protein that modulates MAPK signal cascades. Although MAPK pathways were heavily implicated in prostate cancer progression, the regulation of MAPK8IP2 expression in prostate cancer is not yet reported. We assessed MAPK8IP2 gene expression in prostate cancer related to disease progression and patient survival outcomes. MAPK8IP2 expression was analyzed using multiple genome-wide gene expression datasets derived from The Cancer Genome Atlas (TCGA) RNA-sequence project and complementary DNA (cDNA) microarrays. Multivariable Cox regressions and log-rank tests were used to analyze the overall survival outcome and progression-free interval. MAPK8IP2 protein expression was evaluated using the immunohistochemistry approach. The quantitative PCR and Western blot methods analyzed androgen-stimulated MAPK8IP2 expression in LNCaP cells. In primary prostate cancer tissues, MAPK8IP2 mRNA expression levels were significantly higher than those in the case-matched benign prostatic tissues. Increased MAPK8IP2 expression was strongly correlated with late tumor stages, lymph node invasion, residual tumors after surgery, higher Gleason scores, and preoperational serum prostate-specific antigen (PSA) levels. MAPK8IP2 upregulation was significantly associated with worse overall survival outcomes and progression-free intervals. In castration-resistant prostate cancers, MAPK8IP2 expression strongly correlated with androgen receptor (AR) signaling activity. In cell culture-based experiments, MAPK8IP2 expression was stimulated by androgens in AR-positive prostate cancer cells. However, MAPK8IP2 expression was blocked by AR antagonists only in androgen-sensitive LNCaP but not castration-resistant C4-2B and 22RV1 cells. These results indicate that MAPK8IP2 is a robust prognostic factor and therapeutic biomarker for prostate cancer. The potential role of MAPK8IP2 in the castration-resistant progression is under further investigation.http://www.ajandrology.com/article.asp?issn=1008-682X;year=2023;volume=25;issue=2;spage=198;epage=207;aulast=Huangcell cycle regulation; disease progression; mitogen-activated protein kinase-8-interacting protein 2; patient survival; prostate cancer |
| spellingShingle | Jian Huang Wang Liu Bi-Yun Lin Jean C Li Jane Lu Ben-Yi Li Scaffold protein MAPK8IP2 expression is a robust prognostic factor in prostate cancer associated with AR signaling activity Asian Journal of Andrology cell cycle regulation; disease progression; mitogen-activated protein kinase-8-interacting protein 2; patient survival; prostate cancer |
| title | Scaffold protein MAPK8IP2 expression is a robust prognostic factor in prostate cancer associated with AR signaling activity |
| title_full | Scaffold protein MAPK8IP2 expression is a robust prognostic factor in prostate cancer associated with AR signaling activity |
| title_fullStr | Scaffold protein MAPK8IP2 expression is a robust prognostic factor in prostate cancer associated with AR signaling activity |
| title_full_unstemmed | Scaffold protein MAPK8IP2 expression is a robust prognostic factor in prostate cancer associated with AR signaling activity |
| title_short | Scaffold protein MAPK8IP2 expression is a robust prognostic factor in prostate cancer associated with AR signaling activity |
| title_sort | scaffold protein mapk8ip2 expression is a robust prognostic factor in prostate cancer associated with ar signaling activity |
| topic | cell cycle regulation; disease progression; mitogen-activated protein kinase-8-interacting protein 2; patient survival; prostate cancer |
| url | http://www.ajandrology.com/article.asp?issn=1008-682X;year=2023;volume=25;issue=2;spage=198;epage=207;aulast=Huang |
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