Sex-related hormone receptor in laryngeal squamous cell carcinoma: correlation with androgen estrogen-ɑ and prolactin receptor expression and influence of prognosis

Fei, Mengjia; Zhang, Jingwen; Zhou, Jun; Xu, Yanan; Wang, Jiadong

doi:10.1080/00016489.2017.1373851

Cited by 13 publications

(11 citation statements)

References 17 publications

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“…In recent years, the expression and function of AR and ER in LSCC have been increasingly emphasized. 25 Consistency with our findings, these studies indicate that the sex-related hormone receptors play an important role in the development of LSCC. ER-α and ER-β may be considered as markers for poor biological behavior of laryngeal carcinoma.…”

Section: Discussionsupporting

confidence: 91%

Efficacy of radiation exposure in laryngeal squamous cell carcinoma is mediated by the LAMP3/LAMC2/tenascin-C pathway

Chen

et al. 2019

Exp Biol Med (Maywood)

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The present study explored the role of LAMP3 and related molecular mechanisms in the efficacy of radiation exposure in laryngeal squamous cell carcinoma (LSCC). A lentivirus vector containing the LAMP3 gene was transfected into HEp-2 cells to construct siRNA-LAMP3 and complementation (siLAMP3+LAMP3) groups. Treatment with 4 Gy or 8 Gy radiation was administered to evaluate the role of LAMP3 in radiation therapy. Apoptosis was detected by Annexin V/propidium iodide double staining. Cell migration and invasion were measured in vitro using Transwell and Matrigel assays. Downstream genes regulated by LAMP3 were analyzed using RNA sequencing. Furthermore, a patient-derived xenograft (PDX) model of LSCC was established to verify the efficacy of radiation exposure and the associated signaling pathways downstream of LAMP3. The efficacy of radiation showed that cell proliferation was significantly inhibited by siRNA-LAMP3 knockdown. Increased apoptosis was also observed. Notably, the inhibitory effect was attenuated and apoptosis rates were decreased after LAMP3 complementation. In vitro cellular assays showed that migration and invasion were significantly suppressed by siRNA-LAMP3 knockdown and increased after LAMP3 complementation. Analysis of the efficacy of radiation exposure in the PDX model showed that LAMP3-specific knockdown inhibited tumor growth and that tumor growth was further reduced by the combined radiotherapy treatment. According to transcriptome analysis, the extracellular matrix-receptor interaction pathway is regulated by LAMP3, and further analysis revealed significant differences in key-associated molecules, including laminin subunit gamma-2 (LAMC2) and tenascin-C (TNC). Validation of the in vivo PDX model using qPCR and Western blot analyses supported the abovementioned results. The present findings suggest that reduced LAMP3 expression enhances the efficacy of radiation exposure in LSCC by regulating the LAMP3/LAMC2/TNC signaling pathway. Impact statement It is important to establish effective early diagnostic indicators and reliable treatment strategies for laryngeal squamous cell carcinoma (LSCC). We previously found that expression of LAMP3 was significantly higher in cancerous tissues compared to adjacent normal surgical margin tissues. The present study explored the role of LAMP3 and the related molecular mechanisms in the efficacy of radiation exposure in LSCC. In vitro Transwell and Matrigel assays were performed, and a patient-derived xenograft (PDX) model of LSCC was established. Associated signaling pathways downstream of LAMP3 were analyzed using RNA sequencing. Signaling pathways regulated by LAMP3 were clearly identified by combining the PDX model with transcriptome analysis. Reduced LAMP3 expression enhanced the efficacy of radiation exposure in LSCC. Thus, by utilizing this molecule as a marker, specific groups of patients may be screened for targeted therapy in the future.

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Section: Discussionsupporting

confidence: 91%

Efficacy of radiation exposure in laryngeal squamous cell carcinoma is mediated by the LAMP3/LAMC2/tenascin-C pathway

Chen

et al. 2019

Exp Biol Med (Maywood)

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“…Moreover, PART1 upregulated by androgen is reported to promote cell proliferation and inhibit apoptosis via Toll-like receptor pathway in prostate cancer (Sun et al, 2018). Interestingly, the larynx is also considered a secondary sexual organ and the androgen receptor is highly upregulated in LSCC (Fei et al, 2018). These data indicates that PART1 also play an important role in LSCC.…”

Section: Discussionmentioning

confidence: 99%

Construction and integrated analysis of crosstalking ceRNAs networks in laryngeal squamous cell carcinoma

Liu¹,

Ye²

2019

PeerJ

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Background Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumours of the head and neck. Recent evidence has demonstrated that lncRNAs play important roles in tumour progression and could be used as biomarkers for early diagnosis, prognosis, and potential therapeutic targets. The “competitive endogenous RNA (ceRNA)” hypothesis states that lncRNAs competitively bind to miRNAs through their intramolecular miRNA reaction elements (MREs) to construct a wide range of ceRNA regulatory networks. This study aims to predict the role of ceRNA network in LSCC, for advancing the understanding of underlying mechanisms of tumorigenesis. Material and Methods In this study, the functions of lncRNAs as ceRNAs in LSCC and their prognostic significance were investigated via comprehensive integrated expression profiles data of lncRNAs, mRNAs, and miRNAs obtained from The Cancer Genome Atlas (TCGA). Protein–protein interaction, gene ontology, pathway, and Kaplan–Meier curves analysis were used to profile the expression and function of altered RNAs in LSCC. Results As a result, 889 lncRNAs, 55 miRNAs and 1946 mRNAs were found to be differentially expressed in LSCC. These altered mRNAs were mainly involved in extracellular matrix organization, calcium signaling, and metabolic pathways. To study the regulatory function of lncRNAs, an lncRNA-mediated ceRNA network was constructed. This ceRNA network included 61 lncRNAs, seven miRNAs and seven target mRNAs. Of these RNAs, lncRNAs (TSPEAR-AS, CASK-AS1, MIR137HG, PART1, LSAMP-AS1), miRNA (has-mir-210) and mRNAs (HOXC13, STC2, DIO1, FOXD4L1) had a significant effect on the prognosis of LSCC. Conclusion The results of this study broaden the understanding of the mechanisms by which lncRNAs are involved in tumorigenesis. Furthermore, five lncRNAs (TSPEAR-AS, CASK-AS1, MIR137HG, PART1, LSAMP-AS1) were identified as potential prognostic biomarkers and therapeutic targets for LSCC. These results provide a basis for further experimental and clinical research.

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“…83 An association between estrogen and salivary adenocarcinomas has also been shown recently. 93 The binding of E2 to estradiol receptor α 36 (ERα36) increases larynx SCC proliferation and protection against chemotherapy-induced apoptosis, through a rapid activation of protein kinase C and phospholipase D. Furthermore, in response to E2 activation of ERα36, an upregulation of angiogenic and metastatic factors is observed. This phenomenon induces epithelial-mesenchymal transition.…”

Section: Hormone-induced Carcinogenesis During Pregnancymentioning

confidence: 99%

“…Larynx SCC appears to have a higher expression of androgen, estrogen, prolactin receptors expression than adjacent normal tissues (P < .05). 93 The binding of E2 to estradiol receptor α 36 (ERα36) increases larynx SCC proliferation and protection against chemotherapy-induced apoptosis, through a rapid activation of protein kinase C and phospholipase D. Furthermore, in response to E2 activation of ERα36, an upregulation of angiogenic and metastatic factors is observed. 94 The presence of estrogen receptors in HN cancers occurring during pregnancy has not been studied.…”

Section: Hormone-induced Carcinogenesis During Pregnancymentioning

confidence: 99%

Head and neck cancer during pregnancy

Guévelou

Lebars²,

Kammerer

et al. 2019

Head & Neck

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Background The incidence of cancer during pregnancy is low but is slightly increasing. Data on incidence and etiology of head and neck (HN) cancers in pregnant women are rare. We evaluated the frequency, tumor type, associated factors, and specific biomarkers in HN cancers occurring in pregnant (and peripartum) women. Methods A systematic literature search was performed on PubMed, for any HN tumor site occurring in pregnant women. Results Sixty cases of HN cancers occurring during pregnancy were identified. Most of them were oral cavity cancers. Relationships with oncogenic viruses, hormonal disturbance, and shift in maternal immunity profile were identified. Conclusion Carcinogenesis of HN cancers in pregnant women may be led by different cancer type–specific hallmarks. Relevance of these etiological factors with respect to treatments and birth control recommendations is being investigated by the REFCOR in an ambispective study.

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Sex-related hormone receptor in laryngeal squamous cell carcinoma: correlation with androgen estrogen-ɑ and prolactin receptor expression and influence of prognosis

Abstract: The findings of this study indicate that the sex-related hormone receptors play an important role in the development of LSCC. The PRLR represents a novel prognosticator, because of its negative effect on survival and its interaction with ER-ɑ.

Cited by 13 publications

References 17 publications

Efficacy of radiation exposure in laryngeal squamous cell carcinoma is mediated by the LAMP3/LAMC2/tenascin-C pathway

Efficacy of radiation exposure in laryngeal squamous cell carcinoma is mediated by the LAMP3/LAMC2/tenascin-C pathway

Construction and integrated analysis of crosstalking ceRNAs networks in laryngeal squamous cell carcinoma

Head and neck cancer during pregnancy

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