MEIS-mediated suppression of human prostate cancer growth and metastasis through HOXB13-dependent regulation of proteoglycans

VanOpstall, Calvin; Srikanth, Padma; Brechka, Hannah; Gillard, Marc; Lamperis, Sophia; Zhu, Baizhen; Brown, Roger; Bhanvadia, Raj; Griend, Donald Vander

doi:10.7554/elife.53600

Cited by 33 publications

(32 citation statements)

References 113 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MEIS1 may play a role in limiting the proliferation of NSCLC cells [ 32 ]. In fact, MEIS1 may mediate suppression of metastasis in many types of cancer, including LUAD [ 33 ]. Low expression of MEIS1 in LUAD was consistently observed in the present study, and its favorable effect on LUAD was verified by survival analysis.…”

Section: Discussionmentioning

confidence: 99%

Decreased HLF Expression Predicts Poor Survival in Lung Adenocarcinoma

Wang

Chen

et al. 2021

Med Sci Monit

View full text Add to dashboard Cite

Background Lung adenocarcinoma (LUAD) is a type of non-small cell carcinoma. Its pathogenesis is being explored and there is no cure for the disease. Material/Methods The Gene Expression Omnibus (GEO) was searched to obtain data on expression of messenger RNA. GEO2R, an interactive web tool, was used to calculate the differentially expressed genes (DEGs) in LUAD. All the DEGs from different datasets were imported into VENNY 2.1 ( https://bioinfogp.cnb.csic.es/tools/venny/index.html ) to identify the intersection of the DEGs. An online analysis tool, the Database for Annotation, Visualization, and Integrated Discovery (DAVID), was used to help understand the biological meaning of DEG enrichment in LUAD. Cytoscape 3.7.2 was used to perform centrality analysis and visualize hub genes and related networks. Furthermore, the prognostic value of the hub genes was evaluated with the Kaplan-Meier plotter survival analysis tool. Results The GEO database was used to obtain RNA sequencing information for LUAD and normal tissue from the GSE118370, GSE136043, and GSE140797 datasets. A total of 376 DEGs were identified from GSE118370, 248 were identified from GSE136403, and 718 DEGs were identified from GSE140797. The 10 genes with the highest degrees of expression – the hub genes – were CAV1, TEK, SLIT2, RHOJ, DGSX, HLF, MEIS1, PTPRD, FOXF1 , and ADRB2 . In addition, Kaplan-Meier survival evaluation showed that CAV1, TEK, SLIT2, HLF, MEIS1, PTPRD, FOXF1 , and ADRB2 were associated with favorable outcomes for LUAD. Conclusions CAV1, TEK, SLIT2, HLF, MEIS1, PTPRD, FOXF1 , and ADRB2 are hub genes in the DEG interaction network for LUAD and are involved in the development of and prognosis for the disease. The mechanisms underlying these genes should be the subject of further studies.

show abstract

Section: Discussionmentioning

confidence: 99%

Decreased HLF Expression Predicts Poor Survival in Lung Adenocarcinoma

Wang

Chen

et al. 2021

Med Sci Monit

View full text Add to dashboard Cite

show abstract

“…HOXB13 overexpression (Ov-HOXB13), TEAD4 overexpression (Ov-TEAD4) and pcDNA3.1 negative control (Ov-NC) plasmids were purchased from Shanghai GenePharma Co., Ltd. Briefly, 2x10 4 HGC-27 cells/well were transfected with 100 pmol pcDNA3.1 vectors using Lipofectamine ® 2000 (Invitrogen; Thermo Fisher Scientific, Inc.) according to the manufacturer's protocol. Subsequently, cells were transfected with either small interfering RNA (siRNA) targeting VGLL4 (si-VGLL4-1, 5'-AGG ACC TAG ACT GTG ACA A-3'; si-VGLL4-2, 5'-TCG CAC TGA CCA AGA ACA G-3') or si-NC (5'-CUA GAA CUG GAC AAC GAC A-3') according to the manufacturer's protocol.…”

Section: Methodsmentioning

confidence: 99%

“…The Transwell membranes were precoated with Matrigel, and the substrate membrane was air-dried at room temperature for 3 h and then hydrated with DMEM. Following transfection, 4x10 4 HGC-27 cells/well were seeded into the upper chambers, in serum-free medium. A total of 500 µl complete medium supplemented with 10% FBS was added into the lower chambers as a chemoattractant.…”

Section: Colony Formation Assaymentioning

confidence: 99%

HOXB13 suppresses proliferation, migration and invasion, and promotes apoptosis of gastric cancer cells through transcriptional activation of VGLL4 to inhibit the involvement of TEAD4 in the Hippo signaling pathway

Geng

Liu

et al. 2021

Mol Med Rep

View full text Add to dashboard Cite

Gastric cancer (GC) is one of the most common types of malignancy worldwide and is accompanied by both high mortality and morbidity rates. Homeobox B13 (HOXB13) has been reported to act as a tumor suppressor gene in multiple types of human cancer. The present study aimed to investigate the effects and potential underlying molecular mechanisms of HOXB13 in the progression of GC. The expression of HOXB13 in GC cells was first examined using the Cancer Cell Line Encyclopedia database and subsequently validated in a number of GC cell lines. Following HOXB13 overexpression (Ov-HOXB13), HGC-27 cell proliferation was evaluated by colony formation and Cell Counting Kit-8 assays. Wound healing and Matrigel assays were used to determine the migratory and invasive abilities, respectively. Additionally, cell apoptosis was assessed using TUNEL staining, and the expression of apoptosis-related proteins was detected by western blot analysis. Subsequently, TEA domain transcription factor 4 (TEAD4) was overexpressed to evaluate the effects on HGC-27 cell proliferation, migration, invasion and apoptosis following co-transfection with Ov-HOXB13. The potential binding sites of HOXB13 on the vestigial-like family member 4 (VGLL4) promoter were verified using chromatin immunoprecipitation and dual luciferase reporter assays. Moreover, the expression levels of proteins involved in the Hippo signaling pathway were analyzed using western blotting. The results revealed that the expression of HOXB13 was notably lower in GC cells compared with normal gastric cells. The overexpression of HOXB13 significantly inhibited the proliferation, migration and invasion, but promoted the apoptosis of HGC-27 cells. Moreover, Ov-HOXB13 downregulated TEAD4 expression. Notably, Ov-TEAD4 transfection partially reversed the effects of Ov-HOXB13 on the cellular behaviors of HGC-27 cells. HOXB13 was also confirmed to bind with the VGLL4 promoter. The knockdown of VGLL4 restored the inhibitory effects of Ov-HOXB13 on the expression levels of VGLL4 and Hippo pathway signaling proteins. In conclusion, the findings of the present study suggested that Ov-HOXB13 may suppress the proliferation, migration and invasion, and promote the apoptosis of GC cells through the transcriptional activation of VGLL4 to inhibit the involvement of TEAD4 in the Hippo signaling pathway. These results may provide novel and potent targets for the treatment of GC.

show abstract

“…HOXB13, the most posterior HOXB gene, is expressed in the caudal region of developing embryos, including the tailbud, parts of spine, and hindgut as well as the urogenital sinus, from which the prostate is developed 7 , 8 . In adult prostates, especially in luminal epithelial cells, HOXB13 is highly expressed 9 – 11 . Consistent with the general role of HOX proteins in cell fate determination and tissue differentiation 1 , HOXB13 regulates prostate development and epithelial cell differentiation in normal tissues 9 , 12 .…”

Section: Introductionmentioning

confidence: 99%

Neuroendocrine prostate cancer has distinctive, non-prostatic HOX code that is represented by the loss of HOXB13 expression

Cheng

Yang

Shi

et al. 2021

Sci Rep

View full text Add to dashboard Cite

HOX gene-encoded homeobox proteins control body patterning during embryonic development; the specific expression pattern of HOX genes may correspond to tissue identity. In this study, using RNAseq data of 1019 human cancer cell lines that originated from 24 different anatomic sites, we established HOX codes for various types of tissues. We applied these HOX codes to the transcriptomic profiles of prostate cancer (PCa) samples and found that the majority of prostate adenocarcinoma (AdPCa) samples sustained a prostate-specific HOX code whereas the majority of neuroendocrine prostate cancer (NEPCa) samples did not, which reflects the anaplastic nature of NEPCa. Also, our analysis showed that the NEPCa samples did not correlate well with the HOX codes of any other tissue types, indicating that NEPCa tumors lose their prostate identities but do not gain new tissue identities. Additionally, using immunohistochemical staining, we evaluated the prostatic expression of HOXB13, the most prominently changed HOX gene in NEPCa. We found that HOXB13 was expressed in both benign prostatic tissues and AdPCa but its expression was reduced or lost in NEPCa. Furthermore, we treated PCa cells with all trans retinoic acid (ATRA) and found that the reduced HOXB13 expression can be reverted. This suggests that ATRA is a potential therapeutic agent for the treatment of NEPCa tumors by reversing them to a more treatable AdPCa.

show abstract

MEIS-mediated suppression of human prostate cancer growth and metastasis through HOXB13-dependent regulation of proteoglycans

Cited by 33 publications

References 113 publications

Decreased HLF Expression Predicts Poor Survival in Lung Adenocarcinoma

Decreased HLF Expression Predicts Poor Survival in Lung Adenocarcinoma

HOXB13 suppresses proliferation, migration and invasion, and promotes apoptosis of gastric cancer cells through transcriptional activation of VGLL4 to inhibit the involvement of TEAD4 in the Hippo signaling pathway

Neuroendocrine prostate cancer has distinctive, non-prostatic HOX code that is represented by the loss of HOXB13 expression

Contact Info

Product

Resources

About