MicroRNA17 Post-transcriptional Regulated p21 in Irradiated Betel Quid Chewing Related Oral Squamous Cell Carcinoma Cells

Background: Melatonin, produced by the pineal gland, is known for its antioxidant, oncostatic, and anti-inflammatory properties. However, studies on serum melatonin levels in different cancer types have yielded conflicting results, and little is known about the clinical significance of serum melatonin in oral squamous cell carcinoma (OSCC) in the Southern Asian population. Therefore, we explored its role in OSCC in this study. Methods: A total of 67 male OSCC patients and 78 healthy controls were enrolled in this case–control study. The serum levels of melatonin were determined by enzyme-linked immunosorbent assay (ELISA) and compared between the two groups. Results: The serum melatonin levels were significantly lower in OSCC patients compared with healthy controls (mean ± standard deviation, 15.0 ± 4.6 vs. 18.5 ± 11.8 pg/mL, p = 0.02). In the subgroup of age less than 55 years (mean age of OSCC), OSCC patients had a significantly decreased melatonin level than healthy controls (mean melatonin, 15.7 ± 12.6 vs. 20.8 ± 3.9 pg/mL, p = 0.02). Decreased serum melatonin (odds ratio (OR): 0.95, 95%CI: 0.91–0.99), alcohol consumption (OR: 29.02, 95%CI: 11.68–72.16), betel quid chewing (OR:136.44, 95%CI: 39.17–475.27), and cigarette smoking (OR:29.48, 95%CI: 11.06–78.60) all increased the risk of OSCC under univariate analyses of logistic regression. Betel quid chewing (OR: 45.98, 95%CI: 10.34–204.49) and cigarette smoking (OR:6.94, 95%CI: 1.60–30.16) were the independent risk factors for OSCC in Taiwan. In addition, a negative correlation between age and melatonin level was observed in healthy controls (Pearson r = −0.24, p = 0.03). However, the negative correlation was lost in patients with OSCC. Melatonin concentration had no association with the severity of OSCC. Conclusion: Overall, our study provides evidence that serum melatonin levels decreased in OSCC patients in Taiwan and the decreased level is much significant in young populations and suggests that the decreased melatonin was associated with OSCC, especially in young populations. Further studies are warranted to investigate whether melatonin can be a useful non-invasive screening tool for OSCC.

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Combined Impacts of Genetic Variants of Long Non-Coding RNA MALAT1 and the Environmental Carcinogen on the Susceptibility to and Progression of Oral Squamous Cell Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.684941 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yi-Fang Ding ◽

Yu-Ching Wen ◽

Chun-Yi Chuang ◽

Chiao-Wen Lin ◽

Yi-Chieh Yang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Genetic Variants ◽

Lower Risk ◽

Betel Quid ◽

Environmental Carcinogen ◽

Betel Quid Chewing ◽

Grade Ii

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral cavity, and long non-coding (lnc)RNA of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was recently reported to play a crucial role in OSCC development and progression. However, potential effects of genetic variants of MALAT1 on the development of OSCC are still unclear. Herein, we performed a case-control study in 1350 patients with OSCC and 1199 healthy controls to evaluate the association between functional single-nucleotide polymorphisms (SNPs) of MALAT1 and OSCC susceptibility, as well as its clinicopathologic characteristics. A TaqMan allelic discrimination assay was used to genotype four tagging SNPs, viz., rs3200401 C>T, rs619586 A>G, rs1194338 C>A, and rs7927113 G>A, and results showed that the MALAT1 rs3200401 T allele had a lower risk of OSCC (adjusted odds ratio (AOR): 0.779, 95% confidence interval (CI): 0.632~0.960, p=0.019) and a higher risk of developing moderately (grade II)/poorly (grade III) differentiated OSCC (AOR: 1.508-fold, 95% CI: 1.049~2.169, p=0.027) under a dominant model. According to environmental carcinogen exposure, patients with a betel quid-chewing habit who carried the T allele of rs3200401 more easily developed high-grade (II/III) OSCC (AOR: 1.588, 95% CI: 1.055~2.390, p=0.027), and patients with the same genotype but who did not chew betel quid had a lower risk of developing lymph node metastasis (AOR: 0.437, 95% CI: 0.255~0.749, p=0.003). In addition to rs3200401, the rs619586 AG/GG genotype was associated with increased risks of developing advanced stages (III+IV) and larger tumor sizes (>T2) compared to the AA genotype, especially in the subgroup of betel quid chewers. Furthermore, analyses of clinical datasets revealed that the MALAT1 expression level was upregulated in OSCC compared to normal tissues, especially in the betel quid-chewing population. These results indicated involvement of MALAT1 SNPs rs3200401 and rs619586 in the development of OSCC and support the interaction between MALAT1 gene polymorphisms and the environmental carcinogen as a predisposing factor for OSCC progression.

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