NR4A3 Suppresses Lymphomagenesis through Induction of Proapoptotic Genes

Abstract

Nuclear orphan receptor NR4A1 exerts an essential tumor suppressor function in aggressive lymphomas. In this study, we investigated the hypothesized contribution of the related NR4A family member NR4A3 to lymphomagenesis. In aggressive lymphoma patients, low expression of NR4A3 was associated with poor survival. Ectopic expression or pharmacological activation of NR4A3 in lymphoma cell lines led to a significantly higher proportion of apoptotic cells. In a mouse NSG xenograft model of lymphoma (stably transduced SuDHL4 cells), NR4A3 expression abrogated tumor growth, compared with vector control and uninduced cells that formed massive tumors. Transcript analysis of four different aggressive lymphoma cell lines overexpressing either NR4A3 or NR4A1 revealed that apoptosis was driven similarly by induction of BAK, Puma, BIK, BIM, BID, and Trail. Overall, our results showed that NR4A3 possesses robust tumor suppressor functions of similar impact to NR4A1 in aggressive lymphomas. .

The pro‐inflammatory effect of NR4A3 in osteoarthritis

“…Dysfunction and death of chondrocytes would lead to the failure of articular cartilage . Previous studies showed that NR4A3 is involved in promoting apoptosis in lymphoma and cancer cells by acting as downstream of P53 . Here, our data demonstrated this similar function of NR4A3 in rat chondrocytes (Figure and Figure ).…”

The CXCR4-CXCL12-Axis is of Prognostic Relevance in DLBCL and Its Antagonists Exert Pro-Apoptotic Effects in Vitro

“…In this study, germinal centre B-cells were included as non-neoplastic control and isolated from tonsils from young patients undergoing routine tonsillectomy as described in detail by our research group [50,51]. obtained as colorless solid with a yield of 36%.…”

“…Total RNA from fresh frozen DLBCL patient tissues, non-neoplastic germinal centre B cells and lymphoma cell lines were isolated and cDNA synthesis was performed as previously described by our research group [50,51]. Real-time semi-quantitative PCR (RQ-PCR) for CXCR4, CXCR7, CXCL12, Germany; assays and primers are listed in Table S1) was also performed as previously described [50,51].…”

“…Total RNA from fresh frozen DLBCL patient tissues, non-neoplastic germinal centre B cells and lymphoma cell lines were isolated and cDNA synthesis was performed as previously described by our research group [50,51]. Real-time semi-quantitative PCR (RQ-PCR) for CXCR4, CXCR7, CXCL12, Germany; assays and primers are listed in Table S1) was also performed as previously described [50,51]. GAPDH, ACTB, PPIA, and HPRT1, known to exhibit the lowest variability among lymphoid malignancies [52], were used as housekeeping genes and relative expression was calculated as described by us [50,51].…”

“…Real-time semi-quantitative PCR (RQ-PCR) for CXCR4, CXCR7, CXCL12, Germany; assays and primers are listed in Table S1) was also performed as previously described [50,51]. GAPDH, ACTB, PPIA, and HPRT1, known to exhibit the lowest variability among lymphoid malignancies [52], were used as housekeeping genes and relative expression was calculated as described by us [50,51].…”