MicroRNA-144 suppresses tumorigenesis and tumor progression of astrocytoma by targeting EZH2

Lin, Lvbiao; Zheng, Yungui; Tu, Yanyang; Wang, Zhen; Liu, Hui; Lu, Xiaowen; Xu, Liepeng; Yuan, Jun

doi:10.1016/j.humpath.2015.01.023

Cited by 24 publications

(25 citation statements)

References 27 publications

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“…Numerous studies showed that PRC2 can also have a tumour-suppressive function (reviewed in (14,15)). In numerous experimental settings, it has been established that EZH2 expression and activity are highly regulated at the transcriptional (16–19), posttranscriptional (20–23), and post-translational levels (24–28). Targeting EZH2 is believed to be a promising strategy for cancer therapy (29,30).…”

Section: Introductionmentioning

confidence: 99%

Alternative Splicing of EZH2 pre-mRNA by SF3B3 Contributes to the Tumorigenic Potential of Renal Cancer

Chen

Xiao

Zeng

et al. 2016

Clinical Cancer Research

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Purpose Deregulation or mutation of the EZH2 gene causes various tumors, including ccRCC. Although several splice variants of EZH2 have been identified, little is known about how EZH2 splicing is regulated or the contribution of alternative splicing to its pro-tumorigenic functions. Experimental Design We conducted RT-PCR, western blot and immunohistochemistry techniques, to examine EZH2 and its alternative splicing transcript expression in renal cancer tissue and renal cancer cell lines. Proliferation, migration, clonogenicity and tumorigenicity of renal cancer cells either exhibiting knock-down of EZH2 or its splicing factor SF3B3 were assessed by CCK8, Transwell, and murine xenograft experiments. Results We found that inclusion of alternative EZH2 exon 14 was significantly increased in ccRCC samples and renal cancer cell lines. In ccRCC lines, enforced expression of EZH2Δ14 inhibited, and EZH2 promoted, cell growth, migration, proliferation and tumorigenicity in a xenograft model. Mechanistic studies demonstrated that EZH2Δ14 isoform functions as a dominant-negative inhibitor of full-length EZH2. Coexpression of EZH2Δ14 variant with full-length EZH2 not only abrogated DAB2IP and HOXA9 suppression but also inhibited EZH2-driven tumorigenesis. Strikingly, the splicing factor SF3B3 stimulates inclusion of exon14 and has pro-proliferative activity. Importantly, the upregulation of SF3B3 expression observed in clinical ccRCC samples parallels the increased inclusion of EZH2 exon14, and the SF3B3 level is associated with higher tumor stage and poor overall survival. Conclusions These results suggest that SF3B3 as a key regulator of EZH2 pre-mRNA splicing and SF3B3 may represent a novel prognostic factor and potential therapeutic target in ccRCC.

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Section: Introductionmentioning

confidence: 99%

Alternative Splicing of EZH2 pre-mRNA by SF3B3 Contributes to the Tumorigenic Potential of Renal Cancer

Chen

Xiao

Zeng

et al. 2016

Clinical Cancer Research

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“…Member(s) of the hsa-miR-18114 and hsa-miR-29 families15 exhibit both anticancer and pro-cancer regulation under different clinical conditions, while members of hsa-miR-12616, hsa-miR-12917, hsa-miR-13618, hsa-miR-20419, hsa-miR-66320, hsa-miR-9921, hsa-miR-37822, hsa-miR-9223, and hsa-miR-40924 families are recognized as having anticancer properties under different clinical conditions. Families that contained at least one miRNA found in hAMSC-CM-derived exosomes reportedly exhibit antagonistic roles in numerous cancer types and include hsa-miR-48625, hsa-miR-10026, hsa-miR-10127, hsa-miR-12428, hsa-miR-128529, hsa-miR-13430, hsa-miR-13831, hsa-miR-13932, hsa-miR-14333, hsa-miR-18634, hsa-miR-19335, hsa-miR-20536, hsa-miR-22237, hsa-miR-33838, hsa-miR-33939, hsa-miR-42440, hsa-miR-12741, hsa-miR-2642, hsa-miR-10343, hsa-miR-10744, hsa-miR-12845, hsa-miR-14046, hsa-miR-14447, hsa-miR-15348, hsa-miR-19249, hsa-miR-21250, hsa-miR-21851, hsa-miR-2352, hsa-miR-2553, hsa-miR-37054, hsa-miR-37555, hsa-miR-38156, hsa-miR-41057, hsa-miR-4158, and hsa-miR-9359. These NGS data revealed an enriched miRNA population in hAMSC-CM-derived exosomes that are likely involved in the regulation of different types of cancer.…”

Section: Resultsmentioning

confidence: 99%

“…Exceptionally, hAMSC-CM derived exosomal miRNAs demonstrated outstanding diversity, which encompasses numerous anti-cancer miRNAs891011121314151617181920212223242526272829303132333435363738394041424344454647484950515253545556575859, as well as new and poorly investigated miRNAs. In contrast, miRNAs, which are frequently detected in different cancers exosomes (include hsa-miR-105, hsa-miR-214, hsa-miR-92, hsa-miR-21, hsa-miR-29, hsa-miR-9, hsa-miR-222)6364, were either absent or showed very nominal expression in hAMSC-CM derived exosomes.…”

Section: Discussionmentioning

confidence: 99%

Human adipose mesenchymal stem cell-derived exosomal-miRNAs are critical factors for inducing anti-proliferation signalling to A2780 and SKOV-3 ovarian cancer cells

Reza

Choi

Yasuda

et al. 2016

Sci Rep

186

179

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An enigmatic question exists concerning the pro- or anti-cancer status of mesenchymal stem cells (MSCs). Despite growing interest, this question remains unanswered, and the debate became intensified with new evidences backing each side. Here, we showed that human adipose MSC (hAMSC)-derived conditioned medium (CM) exhibited inhibitory effects on A2780 human ovarian cancer cells by blocking the cell cycle, and activating mitochondria-mediated apoptosis signalling. Explicitly, we demonstrated that exosomes, an important biological component of hAMSC-CM, could restrain proliferation, wound-repair and colony formation ability of A2780 and SKOV-3 cancer cells. Furthermore, hAMSC-CM-derived exosomes induced apoptosis signalling by upregulating different pro-apoptotic signalling molecules, such as BAX, CASP9, and CASP3, as well as downregulating the anti-apoptotic protein BCL2. More specifically, cancer cells exhibited reduced viability following fresh or protease-digested exosome treatment; however, treatment with RNase-digested exosomes could not inhibit the proliferation of cancer cells. Additionally, sequencing of exosomal RNAs revealed a rich population of microRNAs (miRNAs), which exhibit anti-cancer activities by targeting different molecules associated with cancer survival. Our findings indicated that exosomal miRNAs are important players involved in the inhibitory influence of hAMSC-CM towards ovarian cancer cells. Therefore, we believe that these comprehensive results will provide advances concerning ovarian cancer research and treatment.

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“…MiR-144-3p, a well-characterized tumour suppressor, has been reported to suppress cell proliferation in astrocytoma cells [15], bladder cancer and glioblastoma cells [16,17]. Additionally, previous studies have shown that miRNA-144-3p works as a potent osteosarcoma inhibitor [18,19].…”

mentioning

confidence: 99%

MiR‐144‐3p regulates osteogenic differentiation and proliferation of murine mesenchymal stem cells by specifically targeting Smad4

et al. 2016

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Despite extensive research on osteoblast differentiation and proliferation in mesenchymal stem cells (MSCs), the accurate mechanism remains to be further elucidated. MicroRNAs have been reported to be key regulators of osteoblast differentiation and proliferation. Here, we found that miR‐144‐3p is down‐regulated during osteoblast differentiation of C3H10T1/2 cells. Overexpression of miR‐144‐3p inhibited osteogenic differentiation, whereas inhibition of miR‐144‐3p reversed this process. Furthermore, miR‐144‐3p inhibited the proliferation of C3H10T1/2 cells by arresting cells at the G0/G1 phase. Results from bioinformatics analysis, luciferase assay and western blotting demonstrated that miR‐144‐3p directly targeted Smad4. Additionally, Smad4 knockdown blocks the effects of miR‐144‐3p inhibitor. Therefore, we conclude that miR‐144‐3p negatively regulates osteogenic differentiation and proliferation of C3H10T1/2 cells by targeting Smad4.

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MicroRNA-144 suppresses tumorigenesis and tumor progression of astrocytoma by targeting EZH2

Cited by 24 publications

References 27 publications

Alternative Splicing of EZH2 pre-mRNA by SF3B3 Contributes to the Tumorigenic Potential of Renal Cancer

Alternative Splicing of EZH2 pre-mRNA by SF3B3 Contributes to the Tumorigenic Potential of Renal Cancer

Human adipose mesenchymal stem cell-derived exosomal-miRNAs are critical factors for inducing anti-proliferation signalling to A2780 and SKOV-3 ovarian cancer cells

MiR‐144‐3p regulates osteogenic differentiation and proliferation of murine mesenchymal stem cells by specifically targeting Smad4

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