Androgen‐responsive tripartite motif 36 enhances tumor‐suppressive effect by regulating apoptosis‐related pathway in prostate cancer

Abstract

Tripartite motif 36 (TRIM36) belongs to the TRIM family, most members of which are involved in ubiquitination and degradation of target proteins by functioning as E3 ubiquitin ligases. The function of TRIM36 has not been well documented, therefore, we investigated the clinical significance and function of TRIM36 in human prostate cancer (PC). Multivariate logistic regression analysis showed that TRIM36 immunoreactivity was an independent predictor of cancer‐specific survival of PC patients. Gain‐of‐function study revealed that overexpression of TRIM36 suppressed cell proliferation and migration of LNCaP, 22Rv1, and DU145 cells. Moreover, TRIM36 knockdown using siRNA suppressed apoptosis and promoted cell proliferation and migration in LNCaP and 22Rv1 cells. Furthermore, our microarray analysis revealed that the apoptosis‐related pathway was significantly upregulated by TRIM36 overexpression. The TUNEL assay showed that apoptosis promoted by docetaxel treatment was alleviated in siTRIM36‐treated LNCaP and 22Rv1 cells. Taken together, these results suggest that high expression of TRIM36 is associated with favorable prognosis and that TRIM36 plays a tumor‐suppressive role by inhibiting cell proliferation and migration as well as promoting apoptosis in PC.

E3 Ubiquitin Ligase TRIM Proteins, Cell Cycle and Mitosis

“…These TRIMs are often associated with unfavorable prognosis and promote cancer cells proliferation and migration, being often associated with proteins of central signaling pathways. On the other side, TRIMs like TRIM2 [86], TRIM3 [87,88], TRIM15 [89,90], TRIM26 [91], TRIM36 [92] TRIM45 [93], TRIM50 [94], TRIM58 [95,96], and TRIM62 [97] exert a tumor suppressor role, inhibiting cell proliferation and migration as well as promoting apoptosis. Finally, other TRIMs like TRIM32 [98,99,100] and TRIM44 play both an oncogenic and tumor suppressor role in different tumors [101,102,103,104,105,106,107].…”

The Tripartite Nexus: Autophagy, Cancer, and Tripartite Motif-Containing Protein Family Members

“…The androgen receptor possesses a key function in prostate cancer progression serving as the main target for the treatment of advanced, hormone-responsive disease (Yuan et al, 2014). TRIM36 expression is increased in response to androgen and has a prostate cancer suppressive role that includes inhibiting prostate cancer cell proliferation and migration while promoting prostate cancer cell death (Kimura et al, 2018;Liang et al, 2018). Reduced levels of TRIM36 are associated with advanced stages of prostate cancer (Fujimura et al, 2014;Kimura et al, 2018;Liang et al, 2018) and TRIM36 was reported to be an independent predictor of survival in prostate cancer patients (Kimura et al, 2018).…”

“…TRIM36 expression is increased in response to androgen and has a prostate cancer suppressive role that includes inhibiting prostate cancer cell proliferation and migration while promoting prostate cancer cell death (Kimura et al, 2018;Liang et al, 2018). Reduced levels of TRIM36 are associated with advanced stages of prostate cancer (Fujimura et al, 2014;Kimura et al, 2018;Liang et al, 2018) and TRIM36 was reported to be an independent predictor of survival in prostate cancer patients (Kimura et al, 2018). Like TRIM36, expression TRIMs 16 and 29 is decreased in prostate cancer, suggesting that these proteins may act as tumor suppressors in normal prostate tissue.…”

TRIM proteins in neuroblastoma

“…Overexpression of TRIM36 decelerates the cell cycle and limits cell growth [68]. TRIM36 can also act as a putative tumor suppressor by attenuating MAPK/ERK signaling pathways and regulating apoptosis-related pathways in prostate cancer [69,70]. These findings indicate that TRIM36 may have suppressive effects on tumors, specifically in prostate cancer.…”