HMMR is a downstream target of FOXM1 in enhancing proliferation and partial epithelial-to-mesenchymal transition of bladder cancer cells

Dong, Yang; Ma, Yan; Zhao, Pengcheng; Ma, Jing; He, Chaohong

doi:10.1016/j.yexcr.2021.112860

Cited by 16 publications

(16 citation statements)

References 34 publications

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“…Cox univariate and multivariate analyses indicated that the TNM stage and HMMR expression were independent risk factors for LUAD patients resulting in adverse outcomes. Consistent with previous studies, HMMR affects cancer cell proliferation and epithelial-to-mesenchymal transition and results in a poor prognosis (15,31). Our findings strongly confirmed that HMMR can be used as a prognostic biomarker for LAUD.…”

Section: Discussionsupporting

confidence: 92%

“…Our results are consistent with previous studies. HMMR was upregulated in some cancer tissues and was correlated with adverse clinicopathological features and poor prognosis ( 15 , 30 ).…”

Section: Discussionmentioning

confidence: 99%

“…He et al found that HMMR was upregulated in bladder cancer and correlated with poor prognosis. Knockdown of HMMR significantly inhibited bladder cancer growth, invasion, epithelial-to-mesenchymal transition, and inactivation of the Wnt/b-catenin signaling pathway (15). In addition, Fan et al found that the messenger RNA (mRNA) expression of HMMR was significantly increased in hepatocellular carcinoma (HCC) tissues and also correlated with the histologic grade, pathological stage, and survival status.…”

Section: Introductionmentioning

confidence: 99%

“…found that HMMR was upregulated in bladder cancer and correlated with poor prognosis. Knockdown of HMMR significantly inhibited bladder cancer growth, invasion, epithelial-to-mesenchymal transition, and inactivation of the Wnt/β-catenin signaling pathway ( 15 ). In addition, Fan et al.…”

Section: Introductionmentioning

confidence: 99%

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NcRNA-Mediated High Expression of HMMR as a Prognostic Biomarker Correlated With Cell Proliferation and Cell Migration in Lung Adenocarcinoma

et al. 2022

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BackgroundHyaluronan-mediated motility receptor (HMMR) plays a pivotal role in cell proliferation in various cancers, including lung cancer. However, its function and biological mechanism in lung adenocarcinoma (LUAD) remain unclear.MethodsData on HMMR expression from several public databases were extensively analyzed, including the prognosis of HMMR in the Gene Expression Profiling Interactive Analysis (GEPIA) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed using DAVID and gene set enrichment analysis (GSEA) software. The correlation between HMMR expression and immune cell infiltration was analyzed in the Tumor Immune Estimation Resource (TIMER) database, and the gene and protein networks were examined using the GeneMANIA and STRING databases. Experimentally, the expression of HMMR in LUAD and lung cancer cell lines was determined using immunohistochemistry and quantitative RT-PCR assays. Besides, the function of HMMR on cancer cell proliferation and migration was examined using cell growth curve and colony formation, Transwell, and wound healing assays.ResultsIn this study, we found that HMMR was elevated in LUAD and that its high expression was associated with poor clinicopathological features and adverse outcomes in LUAD patients. Furthermore, our results demonstrated that the expression of HMMR was positively correlated with immune cell infiltration and immune modulation. Interestingly, diverse immune cell infiltration affects the prognosis of LUAD. In the functional assay, depletion of HMMR significantly repressed the cancer cell growth and migration of LUAD. Mechanically, we found that that the DNA methylation/TMPO-AS1/let-7b-5p axis mediated the high expression of HMMR in LUAD. Depletion of TMPO-AS1 and overexpression of let-7b-5p could result in the decreased expression of HMMR in LUAD cells. Furthermore, we found that TMPO-AS1 was positively correlated with HMMR, yet negatively correlated with let-7b-5p expression in LUAD.ConclusionsOur findings elucidated that the DNA methylation/TMPO-AS1/let-7b-5p axis mediated the high expression of HMMR, which may be considered as a biomarker to predict prognosis in LUAD.

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Section: Discussionsupporting

confidence: 92%

“…Our results are consistent with previous studies. HMMR was upregulated in some cancer tissues and was correlated with adverse clinicopathological features and poor prognosis ( 15 , 30 ).…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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NcRNA-Mediated High Expression of HMMR as a Prognostic Biomarker Correlated With Cell Proliferation and Cell Migration in Lung Adenocarcinoma

et al. 2022

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“…Initially, HMMR was considered a novel hyaluronan-mediated motility receptor and a microtubule-associated spindle assembly factor 6, 7, 9, 10 . Currently, abundant studies indicate that HMMR plays multiple functional roles in regulating proliferation and metastasis 11 , maintenance of stemness 12 and chemotherapy resistance 13 in various tumours, such as lung cancer 14 , liver cancer 15 , bladder cancer 11 , gastric cancer 16 . Additionally, our previous study found that HMMR was elevated in PCa tumours tissues and associated with poor prognosis 17 .…”

Section: Introductionmentioning

confidence: 99%

HMMR Promotes Prostate Cancer Proliferation and Metastasis via AURKA/mTORC2/E2F1 Positive Feedback Loop

et al. 2022

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Adipocytes Promote Endometrial Cancer Progression Through Activation of the SIRT1‐HMMR Signaling Axis

Savardekar,

Fernandes,

Padhye‐Pendse

et al. 2024

Molecular Carcinogenesis

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Adipocyte is a predominant component of the omental adipose tissue that influences the tumor microenvironment and increases the risk of endometrial cancer progression (EC), however, little is known about the underlying mechanism. In this study, using a co‐culture model, we found that the adipocyte‐EC cell interaction promoted SIRT1 signaling in vitro and in vivo xenograft mice models. Furthermore, immunostaining of SIRT1 protein showed significantly higher expression of SIRT1 in endometrial cancer patients than in normal endometria. RNA sequencing analysis revealed HMMR (hyaluronan‐mediated motility receptor), an oncogene, as a downstream effector of SIRT1 in adipocyte‐associated EC. Transient knockdown and chromatin immunoprecipitation assays showed that SIRT1 inhibition impedes transcription of the HMMR gene via FOXM1, and reduced expression of HMMR in co‐cultured EC cells blocks AURKA activation via TPX2, leading to cell cycle arrest. This is the first study to report the positive correlation between SIRT1 and HMMR in EC patient tumors and might be used as a potential biomarker in EC. Notably, SIRT1 regulates HMMR expression in a FOXM1‐dependent manner, and interfering with SIRT1 may provide a promising strategy for the management of endometrial cancer.

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HMMR is a downstream target of FOXM1 in enhancing proliferation and partial epithelial-to-mesenchymal transition of bladder cancer cells

Cited by 16 publications

References 34 publications

NcRNA-Mediated High Expression of HMMR as a Prognostic Biomarker Correlated With Cell Proliferation and Cell Migration in Lung Adenocarcinoma

NcRNA-Mediated High Expression of HMMR as a Prognostic Biomarker Correlated With Cell Proliferation and Cell Migration in Lung Adenocarcinoma

HMMR Promotes Prostate Cancer Proliferation and Metastasis via AURKA/mTORC2/E2F1 Positive Feedback Loop

Adipocytes Promote Endometrial Cancer Progression Through Activation of the SIRT1‐HMMR Signaling Axis

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