Androgen Receptor as a Biomarker of Oral Squamous Cell Carcinoma Progression Risk

Tomasović-Lončarić, Čedna; Fučić, Aleksandra; Andabak, Ana; Andabak, Matej; Ceppi, Marcello; Bruzzone, Marco; Vrdoljak, Danko Velemir; Vučićević-Boras, Vanja

doi:10.21873/anticanres.13593

Cited by 18 publications

(11 citation statements)

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“…The identification of sensitive biomarkers was very important for the improvements of the clinical outcome of OSCC patients [21,22]. There have been many papers reporting the discovery of OSCC biomarkers, but only a few biomarkers have been validated and successfully applied in routine clinical practice [23,24]. Moreover, most biomarkers possess limitations for the early detection of OSCC, and their prognostic value was plagued by inaccuracies.…”

Section: Discussionmentioning

confidence: 99%

lncRNA TSPEAR-AS2, a Novel Prognostic Biomarker, Promotes Oral Squamous Cell Carcinoma Progression by Upregulating PPM1A via Sponging miR-487a-3p

et al. 2021

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Background. Long noncoding RNA (lncRNA) critically impacts the modulation of tumor developments and progressions. Our study is aimed at investigating the expressing patterns, clinical significance, and biological roles of lncRNA TSPEAR-AS2 (TSPEAR-AS2) in oral squamous cell carcinoma (OSCC). Material and Approach. The expressing states achieved by TSPEAR-AS2 were examined in OSCC specimens and cell lines by RT-PCR. The clinical significance of TSPEAR-AS2 was statistically analyzed. OSCC proliferating, invading, and migrating processes were examined with the use of wound healing assays, transwell, colony formation, and cell counting kit-8. Additionally, the downstream molecular mechanism of TSPEAR-AS2 in OSCC was explored. Results. TSPEAR-AS2 was overexpressed in OSCC tumors and cells. High TSPEAR-AS2 was associated with advanced TNM stage. Patients with high TSPEAR-AS2 expression displayed a shorter disease-free survival and total survival of OSCC patients than those with low TSPEAR-AS2 expressing level. It was found that knockdown of TSPEAR-AS2 could inhibit the proliferating, invading, and migrating processes pertaining to OSCC cells. Luciferase reporter tests and RNA pull-down results revealed that TSPEAR-AS2 enhanced the expressions of PPM1A by regulating miR-487a-3p, and TSPEAR-AS2 could be adopted as a miR-487a-3p sponge to inhibit PPM1A expression. Conclusion. Our study highlighted the significance of the TSPEAR-AS2/miR-487a-3p/PPM1A axis within OSCC progression and offered a novel biomarker and novel strategies for OSCC treatments.

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Section: Discussionmentioning

confidence: 99%

lncRNA TSPEAR-AS2, a Novel Prognostic Biomarker, Promotes Oral Squamous Cell Carcinoma Progression by Upregulating PPM1A via Sponging miR-487a-3p

et al. 2021

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“…Effective tumor markers can reduce tumor recurrence rate and increase survival rate; finding such markers could provide important guidance for clinical treatment [25]. Even though many new OSCC biomarkers have been identified in recent years [26][27][28], their mechanisms remain unclear. As an emerging tumor biomarker, LINC01303 has been extensively studied, but its role in OSCC is unknown.…”

Section: Discussionmentioning

confidence: 99%

LncRNA LINC01303 Promotes the Progression of Oral Squamous Cell Carcinomas via the miR-429/ZEB1/EMT Axis

Sun

Zheng

et al. 2021

Journal of Oncology

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Objectives. The aim of this research was to uncover the biological role and mechanisms of LINC01303 in oral squamous cell carcinoma (OSCC). Materials and Methods. Real-time quantitative PCR (qRT-PCR) was used to determine LINC01303 expression in OSCC tissues. Subcellular distribution of LINC01303 was examined by nuclear/cytoplasmic RNA fractionation and FISH experiments. The role of LINC01303 in the growth of TSCCA and SCC-25 was examined by CCK-8 assay, colony formation, transwell invasion assay in vitro, and xenograft tumor experiment in vivo. Dual-luciferase reporter assay was used to verify the interaction between LINC01303 and miR-429. RNA pull‐down assay was used to discover miR-429‐interacted protein, which was further examined by qRT-PCR, western blot, and rescue experiments. Results. LINC01303 expression was higher in OSCC tissues compared with adjacent nontumor tissues. LINC01303 was found to be localized in the cytoplasm of OSCC cells. Knockdown of LINC01303 inhibited OSCC cell proliferation and invasion, whereas increasing the expression of LINC01303 showed the opposite effects. Furthermore, LINC01303 served as a miR-429 “sponge” and positively regulated ZEB1 expression. Moreover, LINC01303 promoted OSCC through miR-429/ZEB1 axis both in vivo and in vitro. Conclusions. LINC01303 plays an oncogenic role in OSCC and is a promising biomarker for OSCC patients.

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“…Those in vitro observations also associated AR signalling with enhanced cell migration, potentially increasing tumour aggressiveness. Another recent study using a larger cohort (total n=196) of metastatic and non-metastatic OSCC patients suggested that AR cytoplasmic accumulation associates with moderately increased risk of metastasis (78). The significance of AR cytoplasmic immunostaining in this context requires additional clarification, especially considering that AR splice variants play an important role in prostate cancer and some of those variants may accumulate in the cytoplasm (Zhan et al, 2017) (79).…”

Section: Hormone Receptors In Hnsccmentioning

confidence: 99%

Is There a Role for Sex Hormone Receptors in Head-and-neck Cancer? Links with HPV Infection and Prognosis

et al. 2021

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Background/Aim: Head-and-neck squamous cell carcinoma (HNSCC) is the fifth most common cancer in the world and human papillomavirus (HPV) is an important risk factor for this neoplasm. Recent studies showed an association between sex hormone receptors and pathogenesis and/or prognosis in patients with HNSCC. The aim of this study was to clarify the expression patterns of sex hormone receptors in HPV-positive and HPV-negative HNSCC and their associations with tumour biopathology and biological behaviour. Materials and Methods: Scientific literature indexed in PubMed about sex hormone receptors in HNSCC was retrieved and critically analyzed, to obtain an overview of expression patterns and their possible implications for tumour biopathology and prognosis. Results: Sex hormone receptors were more frequently detected in oropharyngeal tumours compared with HNSCC from other locations. ERα was associated with HPV-positive tumours. The androgen and progesterone receptors were associated with poor patient prognosis. Estrogen receptor alpha (ERα) is implicated in the biopathology of HNSCC in different ways, by promoting DNA hypermutation and facilitating HPV integration thus contributing to an immunogenic phenotype, but also by cooperating with the epithelial growth factor receptor (EGFR) to promote resistance to therapy. Conclusion: The expression of sex hormone receptors may be of prognostic value in specific tumour subgroups, but the use of hormonal therapies for HNSCC is still not in close sight.Head-and-neck cancer comprises a group of malignancies affecting multiple sites including the oral cavity, the oropharynx, nasopharynx, hypopharynx, larynx and the salivary glands. Histologically, these lesions are most commonly squamous cell carcinomas (HNSCC) (1). An estimated 650,000 new cases occur yearly worldwide, along with 330 000 deaths from HNSCC (2). In the USA, HNSCC corresponds to 3% of all cancers with approximately 53,000 new cases and 10,800 deaths yearly. Males seem to be at higher risk, with a male to female ratio varying between 2:1 and 4:1 (3). Classically, alcohol and tobacco consumption have been identified as major risk factors for developing HNSCC (4, 5). Recently, infection with high-risk human papillomavirus (HPV) has been recognized as a risk factor for developing HNSCC (6). HPVpositive HNSCC is preferentially located at oropharyngeal sites, especially the tonsils and the tongue base, and shows distinguishing clinico-pathological features (7). Other risk factors for developing HNSCC include dietary or workplace exposure to environmental toxicants and genetic predisposition (8-10). Between 2005 and 2014, the incidence of HPV-positive HNSCC increased by 3% while that of classical lesions decreased by 2% (11). The increasing incidence of HPVpositive HNSCC motivated a significant effort to understand the biopathology of these lesions and adapt the current therapeutic approaches (12). A number of markers is currently in use or under study for identifying these lesions (e.g., immunohistochemistry for p16 IN...

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Androgen Receptor as a Biomarker of Oral Squamous Cell Carcinoma Progression Risk

Cited by 18 publications

References 35 publications

lncRNA TSPEAR-AS2, a Novel Prognostic Biomarker, Promotes Oral Squamous Cell Carcinoma Progression by Upregulating PPM1A via Sponging miR-487a-3p

lncRNA TSPEAR-AS2, a Novel Prognostic Biomarker, Promotes Oral Squamous Cell Carcinoma Progression by Upregulating PPM1A via Sponging miR-487a-3p

LncRNA LINC01303 Promotes the Progression of Oral Squamous Cell Carcinomas via the miR-429/ZEB1/EMT Axis

Is There a Role for Sex Hormone Receptors in Head-and-neck Cancer? Links with HPV Infection and Prognosis

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