MiR-378a-3p Is Critical for Burkitt Lymphoma Cell Growth

Niu, Fubiao; Dzikiewicz‐Krawczyk, Agnieszka; Koerts, Jasper; Jong, Debora de; Wijenberg, L; Hernandez, Margot Fernandez; Ślęzak-Prochazka, Izabella; Winkle, Melanie; Kooistra, Wierd; Sluis, Tineke van der; Rutgers, Bea; Terpstra, Miente Martijn; Kok, Klaas; Kluiver, Joost; Berg, Anke van den

doi:10.3390/cancers12123546

Cited by 15 publications

(12 citation statements)

References 58 publications

(71 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although miR-378a-3p has been reported as either an oncogenic or tumor suppressive microRNA in different cancers [30][31][32], we herein observed a tumor suppressive effect of miR-378a-3p on PCa cell proliferation and metastasis when EVs release was inhibited by GW4869. Combined with other ndings indicating a lower endogenous concentration of mature miR-378a-3p but a similar one of primary miR-378a-3p precursors in PCa cells vs. BPH cells, we hypothesized that tumor-derived EVs mediated the release of miR-378a-3p for maintenance of the malignant phenotype of PCa cells.…”

Section: Discussioncontrasting

confidence: 53%

Tumor-Derived miR-378a-3p-Containing Extracellular Vesicles Promote Osteolysis by Activating a Dyrk1a/Nfatc1/Angptl2 Axis for Bone Metastasis

Wang

et al. 2021

Preprint

View full text Add to dashboard Cite

Background The majority of the deaths of prostate cancer (PCa) are caused by progression to bone metastatic PCa. The importance of extracellular vesicles (EVs) in the formation of the pre-metastatic niche has been demonstrated in recent years. However, whether and how tumor-derived EVs interact with bone marrow macrophages (BMMs) to release EV-delivered microRNAs to promote osteolysis and to activate pre-metastatic niche formation for PCa bone metastasis remain unclear. Methods Bioinformatics and qRT-PCR analyses were used to screen microRNAs and to identify the elevated expression of miR-378a-3p in both serum-derived EVs from PCa patients and in culture medium-derived EVs from PCa cell lines. Functional assays in vitro and in vivo were performed to investigate the functions of miR-378a-3p during PCa progression. IF staining and Dual-luciferase reporter, co-IP, western blot, RIP and ChIP assays were conducted to reveal the underlying mechanism. Results We found that EV-mediated release of miR-378a-3p from tumor cells was upregulated in bone-metastatic PCa which keeps a low intracellular concentration of miR-378a-3p, to promote proliferation and the MAOA-mediated epithelial-to-mesenchymal transition (EMT) in PCa cells. In addition, we demonstrated that the enrichment of miR-378a-3p in tumor derived EVs was induced by overexpression of hnRNPA2B1 as a transfer chaperone. After miR-378a-3p-enriched EVs were taken in by BMMs, elevated intracellular concentration of miR-378a-3p promoted osteolytic progression by targeting the Dyrk1a/Nfatc1 pathway. Mechanistically, inhibition of Dyrk1a by miR-378a-3p improved the nuclear translocation of Nfatc1 to promote expression of the downstream target gene Angptl2. As a feedback, increased secretion of Angptl2 into the tumor environment promoted PCa progression. Conclusions Our findings indicate that tumor-derived miR-378a-3p-containing EVs play a significant role in promoting prostate cancer bone metastasis by activating a Dyrk1a/Nfatc1/Angptl2 axis in BMMs to induce osteolytic progression, which implicates that miR-378a-3p may be a potential predictor of metastatic PCa. Moreover, reducing the release of miR-378a-3p-containing EVs or inhibiting the recruitment of miR-378a-3p into tumor-derived EVs might be a potential therapeutic strategy for PCa metastasis.

show abstract

Section: Discussioncontrasting

confidence: 53%

Tumor-Derived miR-378a-3p-Containing Extracellular Vesicles Promote Osteolysis by Activating a Dyrk1a/Nfatc1/Angptl2 Axis for Bone Metastasis

Wang

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Niu et al [ 71 ] described that MYC induced miR-378a-3p , which, in turn, down-regulated MNT in Burkitt’s lymphoma. MNT reduction releases MNT–MYC antagonism and enables the MYC-driven transformation process.…”

Section: Functions Of Mnt In the Cellmentioning

confidence: 99%

The Multiple Faces of MNT and Its Role as a MYC Modulator

Liaño-Pons

Arsenian-Henriksson

León

2021

Cancers

View full text Add to dashboard Cite

MNT is a crucial modulator of MYC, controls several cellular functions, and is activated in most human cancers. It is the largest, most divergent, and most ubiquitously expressed protein of the MXD family. MNT was first described as a MYC antagonist and tumor suppressor. Indeed, 10% of human tumors present deletions of one MNT allele. However, some reports show that MNT functions in cooperation with MYC by maintaining cell proliferation, promoting tumor cell survival, and supporting MYC-driven tumorigenesis in cellular and animal models. Although MAX was originally considered MNT’s obligate partner, our recent findings demonstrate that MNT also works independently. MNT forms homodimers and interacts with proteins both outside and inside of the proximal MYC network. These complexes are involved in a wide array of cellular processes, from transcriptional repression via SIN3 to the modulation of metabolism through MLX as well as immunity and apoptosis via REL. In this review, we discuss the present knowledge of MNT with a special focus on its interactome, which sheds light on the complex and essential role of MNT in cell biology.

show abstract

“…Thus, it is important to investigate the role of miR-378a-3p in regulating HCC angiogenesis to develop therapeutic interventions. Several studies have shown that miR-378a-3p plays different functions in different tumors [23,[36][37][38][39][40]. In this study, we found that the expression of miR-378a-3p was downregulated in HCC and was related to the poor prognosis.…”

Section: Discussionmentioning

confidence: 50%

DNMT1-Induced miR-378a-3p Silencing Promotes Angiogenesis via NF-κB Signaling Pathway by Targeting TRAF1 in Hepatocellular Carcinoma

Zhu

Chen

Feng

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Angiogenesis plays an important role in the occurrence, development and metastasis of hepatocellular carcinoma (HCC). miR-378a-3p participates in tumorigenesis and tumor metastasis according to previous studies, yet the exact role it plays in HCC angiogenesis remains poorly understood.Methods: qRT-PCR was used to investigate the expression of miR-378a-3p in HCC tissues and cell lines. The effects of miR-378a-3p on HCC in vitro and in vivo were examined by CCK-8, transwell assay, tube formation and matrigel plug assay. RNA sequencing, bioinformatics analysis, luciferase reporter assay, immunofluorescence assay and ChIP assay were used to detected the molecular mechanism of miR-378a-3p-induced inhibition of angiogenesis. Results: We confirmed that the expression of miR-378a-3p was significantly downregulated and was associated with microvascular density (MVD) in HCC, which indicated a short survival time of HCC patients, and reducing miR-378a-3p expression led to a significant increase in angiogenesis in vitro and in vivo. miR-378a-3p directly targeted TNF receptor associated factor 1 (TRAF1) to attenuate NF-κB signaling, and then decreases secreted vascular endothelial growth factor (VEGF). DNA methyltransferase 1 (DNMT1) mediated hypermethylation of miR-378a-3p was responsible for downregulating of miR-378a-3p. Moreover, a series of investigation indicated that p65 initiated a positive feedback loop, which could up-regulate DNMT1 to promote hypermethylation of the miR-133a-3p promoter.Conclusion: Our study indicates that a novel DNMT1/miR-378a-3p/TRAF1/ NF-κB positive feedback loop in HCC cells, which may become a potential therapeutic target for HCC.

show abstract

MiR-378a-3p Is Critical for Burkitt Lymphoma Cell Growth

Cited by 15 publications

References 58 publications

Tumor-Derived miR-378a-3p-Containing Extracellular Vesicles Promote Osteolysis by Activating a Dyrk1a/Nfatc1/Angptl2 Axis for Bone Metastasis

Tumor-Derived miR-378a-3p-Containing Extracellular Vesicles Promote Osteolysis by Activating a Dyrk1a/Nfatc1/Angptl2 Axis for Bone Metastasis

The Multiple Faces of MNT and Its Role as a MYC Modulator

DNMT1-Induced miR-378a-3p Silencing Promotes Angiogenesis via NF-κB Signaling Pathway by Targeting TRAF1 in Hepatocellular Carcinoma

Contact Info

Product

Resources

About