Understanding patterns of invasion: a novel approach to assessment of podoplanin expression in the prediction of lymph node metastasis in oral squamous cell carcinoma

Sharma, Ankita; Boaz, Karen; Natarajan, Srikant

doi:10.1111/his.13416

Cited by 13 publications

(15 citation statements)

References 20 publications

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“…Oral squamous cell carcinoma (OSCC) accounts for more than 95% of all head and neck cancer and ranks among the top eight causes of cancer-related death globally 1,2 . The deadliest aspect of oral cancer is metastasis 3,4 .…”

Section: Introductionmentioning

confidence: 99%

circRNA_0000140 suppresses oral squamous cell carcinoma growth and metastasis by targeting miR-31 to inhibit Hippo signaling pathway

et al. 2020

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Oral squamous cell carcinoma (OSCC) is one of the most common malignancies and has a poor prognosis. Circular RNA (circRNA) has been increasingly recognized as a crucial contributor to carcinogenesis. circRNA_0000140 has been aberrantly expressed in OSCC, but its role in tumor growth and metastasis remains largely unclear. Sanger sequencing, actinomycin D, and RNase R treatments were used to confirm head-to-tail junction sequences and the stability of circ_0000140. In vitro cell activities, including proliferation, migration, invasion, and apoptosis, were determined by colony formation, transwell, and flow cytometry assays. The expression levels of circ_0000140, Hippo signaling pathway, and serial epithelial-mesenchymal transition (EMT) markers were measured by quantitative real-time PCR, western blotting, immunofluorescence, and immunohistochemistry. Dual luciferase reporter assays and Argonaute 2-RNA immunoprecipitation assays were performed to explore the interplay among circ_0000140, miR-31, and LATS2. Subcutaneous tumor growth was observed in nude mice, in which in vivo metastasis was observed following tail vein injection of OSCC cells. circ_0000140 is derived from exons 7 to 10 of the KIAA0907 gene. It was down-regulated in OSCC tissues and cell lines, and correlated negatively with poor prognostic outcomes in OSCC patients. Gain-offunction experiments demonstrated that circ_0000140 enhancement suppressed cell proliferation, migration, and invasion, and facilitated cell apoptosis in vitro. In xenograft mouse models, overexpression of circ_0000140 was able to repress tumor growth and lung metastasis. Furthermore, mechanistic studies showed that circ_0000140 could bind with miR-31 and up-regulate its target gene LATS2, thus affecting OSCC cellular EMT. Our findings demonstrated the roles of circ_0000140 in OSCC tumorigenesis as well as in metastasis, and circ_0000140 exerts its tumor-suppressing effect through miR-31/LATS2 axis of Hippo signaling pathway in OSCC.

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Section: Introductionmentioning

confidence: 99%

circRNA_0000140 suppresses oral squamous cell carcinoma growth and metastasis by targeting miR-31 to inhibit Hippo signaling pathway

et al. 2020

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“…In spite of considerable advances being made in diagnostics and treatment, the 5-year survival rate for patients with OSCC has not improved during the past few decades and remains <50% (2). Although much scientific research has indicated that local recurrence and nodal metastasis are the major causes of mortality in patients with OSCC, the precise molecular mechanisms remain unclear (3)(4)(5). Therefore, in order to improve the diagnosis and management of patients with OSCC, it is important to identify effective diagnostic biomarkers and therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA H1 promotes cell proliferation and invasion by acting as a ceRNA of miR‑138 and releasing EZH2 in oral squamous cell carcinoma

Hong

Sui

et al. 2018

Int J Oncol

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Long non-coding RNAs (lncRNAs) have been shown to play pivotal roles in various types of human cancer, including oral squamous cell carcinoma (OSCC). However, the potential mechanisms of action of lncRNAs in OSCC remain to be fully elucidated. The aim of the present study was to further explore the potential mechanisms of action of lncRNAs in OSCC. We first analyzed Gene Expression Omnibus (GEO) datasets to investigate aberrantly expressed lncRNAs which may be involved in the development of OSCC. Reverse transcription‑quantitative PCR (RT‑qPCR) was performed to analyze the expression levels of lncRNA H19. In addition, the correlation between H19 expression and the clinical characteristics and prognosis of patients with OSCC was statistically analyzed. The effects of H19 expression on OSCC cells were examined by using overexpression and RNA interference approaches in vitro and in vivo. To examine the competitive endogenous RNA (ceRNA) mechanisms, bioinformatics analysis and luciferase reporter assay were performed. In addition, the correlation between H19 and microRNA (miR)‑138 was detected. H19 was found to be upregulated in OSCC tissues and its high expression level was associated with the TNM stage and nodal invasion, and also correlated with a shorter overall survival of patients with OSCC. The knockdown of H19 significantly inhibited OSCC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), and induced apoptosis in vitro; it also suppressed subcutaneous tumor growth in vivo. In addition, H19 was found to regulate the expression of oncogene enhancer of zeste homolog 2 (EZH2) by competing with miR‑138; the inhibition of miR‑138 attenuated the inhibitory effects of H19 knockdown on OSCC cells. On the whole, our findings suggest that H19 functions as an oncogene by inhibiting miR‑138 and facilitating EZH2 expression in OSCC. Thus, lncRNA H1 may represent a potential therapeutic target for OSCC.

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“…The search strategy resulted in 721 records without duplicates. After full‐text reading, 58 studies were excluded (Appendix ) and 29 7,8,10,20‐45 were included (Figure 1). The same tissue samples were used in two included studies 23,29 (confirmed by personal communication, Dr Denise Oliveira, April 30, 2019).…”

Section: Resultsmentioning

confidence: 99%

Prognostic and clinicopathological significance of podoplanin immunoexpression in oral and oropharyngeal squamous cell carcinoma: A systematic review

Mello

Kammer

Silva

et al. 2020

J Oral Pathology Medicine

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Background Podoplanin (PDPN) is a glycoprotein associated with epithelial‐mesenchymal transition, invasion, and metastasis in several types of malignancies, including oral and oropharyngeal squamous cell carcinoma (OSCC). The aim of this systematic review (SR) was to summarize and critically appraise the available evidence about the association between PDPN immunoexpression and clinicopathological features and its utility as a prognostic marker in OSCC. Methods Five electronic databases and three gray literature databases were searched for immunohistochemical studies, which were selected in a two‐phase process. Results From 721 records identified, 22 cohort and seven analytical cross‐sectional studies were included. Few studies reported that PDPN expression was associated with poorer survival rates in OSCC: overall survival = 4/12, disease‐free survival = 4/7, and cancer‐specific survival = 2/4 studies. Positive associations were most frequently reported on lymph node involvement, higher histopathological grade, and advanced clinical stages. Conclusion Within limitations of this SR, PDPN may be associated with lymph node involvement, histopathological grade, and clinical stage of OSCC. Current evidence suggests that PDPN could be a useful prognostic marker for OSCC that needs further exploration.

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Understanding patterns of invasion: a novel approach to assessment of podoplanin expression in the prediction of lymph node metastasis in oral squamous cell carcinoma

Cited by 13 publications

References 20 publications

circRNA_0000140 suppresses oral squamous cell carcinoma growth and metastasis by targeting miR-31 to inhibit Hippo signaling pathway

circRNA_0000140 suppresses oral squamous cell carcinoma growth and metastasis by targeting miR-31 to inhibit Hippo signaling pathway

Long non-coding RNA H1 promotes cell proliferation and invasion by acting as a ceRNA of miR‑138 and releasing EZH2 in oral squamous cell carcinoma

Prognostic and clinicopathological significance of podoplanin immunoexpression in oral and oropharyngeal squamous cell carcinoma: A systematic review

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