Altered expression of striatin‑4 is associated with poor prognosis in bladder transitional cell carcinoma

Abstract

Striatin-4 (STRN4 or Zinedin) is a scaffolding protein belonging to the mammalian STRN family of proteins and consists of multiple functional signaling domains. Due to its numerous signaling complexes, STRN4 has been reported to be involved in the tumorigenesis of various cancer types, including colon cancer, liver cancer and prostate cancer. However, few studies on STRN4 have been conducted in bladder cancer, and its prognostic role in bladder cancer remains unknown. The present study aimed to investigate the expression levels of STRN4 in bladder transitional cell carcinoma and evaluate the prognostic role of STRN4. STRN4 expression in clinical specimens was analyzed using immunohistochemistry and reverse transcription-quantitative PCR. It was demonstrated that STRN4 expression was significantly associated with clinical parameters such as tumor size, muscle invasion depth and pathological tumor grade. Abnormal STRN4 expression was typically associated with worse overall survival time and outcome when compared with the low STRN4 expression group. Using multivariate analysis, it was reported that STRN4 was an independent prognostic biomarker for survival time in bladder transitional cell carcinoma. Although the specific biological mechanisms of STRN4 in bladder cancer still remain to be elucidated, STRN4 expression could be a prognostic indicator in bladder cancer.

Plasma circulating microRNAs associated with blood-based immune markers: a population-based study

“…Both STRN and ATP6V1G3 are validated targets of miR-342-3p. STRN has multiple functional signaling complexes which are reportedly involved in the tumorigenesis of various cancers [ 45 ]. miR-342-3p additionally targets ATP6V1G3 , an integral protein-coding gene for the regulation of membrane transport, which has also been identified as an immunohistochemical marker for different cancers [ 46 ].…”

Biased holoenzyme assembly of protein phosphatase 2A (PP2A): From cancer to small molecules

“…The therapeutic targeting of phosphatases, like PP2A, to reestablish cellular homeostasis has been limited by the structural diversity of this family of enzymes. Complicating this approach further, as explained previously, is that certain PP2A holoenzymes are important for its tumor-suppressive activity, while other holoenzymes promote oncogenic transformation (such as STRN4) ( 44 , 63 , 64 , 80 , 83 , 142 , 143 , 144 , 145 ). Thus, there is a need for a more comprehensive understanding of the role of each holoenzyme complex in cancer, as well as high resolution structures of each heterotrimer to allow for specific therapeutic targeting of disease relevant PP2A heterotrimers.…”

“…Striatin 3 upregulation resulted in hyperactivation of YAP1, leading to loss of Hippo tumor-suppressive functions, which ultimately correlated with poor prognosis in a cohort gastric cancer patients ( 143 ). Lastly, Striatin 4 has been documented to be highly expressed in a variety of cancers, and studies have shown that depleting its expression leads to a reduction in proliferation, invasion, and metastasis both in vitro and in vivo ( 144 , 145 ). As mentioned previously, Striatin 4 was recruited by SV40 ST to the Striatin Interacting Phosphatase and Kinase (STRIPAK) complex that redirects PP2A function toward the dephosphorylation of MAP4K4, leading to the activation of YAP1 and the inactivation of Hippo tumor-suppressive function ( 44 ).…”

Cellular Impacts of Striatins and the STRIPAK Complex and Their Roles in the Development and Metastasis in Clinical Cancers (Review)

“…In bladder cancer development, CCM3 was identified as a downstream target of anti-tumourigenic miR-26a-5p and miR-26b-5p. Both miRs were dysregulated in bladder cancer, leading to the upregulation of CCM3, which promotes proliferation of bladder cancer cells in vitro [ 103 ] CCM3 was further reported to have clinical significance [ 45 , 103 ], similar to STRN4, which was found to have elevated expression in bladder cancer tissue compared to adjacent normal tissue and was significantly associated with several clinicopathological factors of patients [ 102 ].…”