Vitamin D inhibits the proliferation of Oral Squamous Cell Carcinoma by suppressing lncRNA LUCAT1 through the MAPK pathway

Abstract

Background: Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer worldwide. Recent studies have suggested that vitamin D (VitD) is associated with a reduced risk of many chronic illnesses, including cancer. However, the role of vitamin D in OSCC has rarely been reported.

Materials and Methods: The effect of vitamin D and control treatment were examined by cell clone formation assay. Using RNA-seq, we globally identified VitD-regulated long noncoding RNAs (lncRNAs). The expression of LUCAT1 in OSCC tissues and cell lines was examined by qRT-PCR. The correlation between LUCAT1 expression level and clinicopathological characteristics was analyzed. The biological roles of LUCAT1 in OSCC cell proliferation was determined by CCK8 and cell colony formation. The role of LUCAT1 in OSCC growth was further confirmed by mouse xenograft tumor model. Combined with the literature, the mechanism of action of LUICAT1 was verified by western blot.

Results: In this study, we observed that VitD inhibited tumour cell growth in OSCC. We found that lncRNA LUCAT1 was downregulated by VitD and served as an important mediator of VitD in inhibiting OSCC cell proliferation. Moreover, we observed that the expression of LUCAT1 was significantly upregulated in OSCC tissues compared to non-tumour tissues. We further demonstrated that LUCAT1 promoted the proliferation of oral cancer cells by enhancing the activation of the mitogen protein kinase (MAPK) signalling pathway.

Conclusion: In summary, our results show that VitD inhibited the growth of OSCC cells through the LUCAT1-MAPK signalling pathway. Our study suggested that VitD could suppress the progression of oral cancer, and LUCAT1 may be a potential tumour marker for the diagnosis and prognosis of OSCC.

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See also:

- Official Web Site: The Di Bella Method;

- The Di Bella Method (A Fixed Part - Dihydrotachysterol, Alfacalcidol, synthetic Vitamin D3);

- Vitamin D (analogues and/or derivatives) and cancer - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - All-Trans Retinoic Acid, Analogues and/or Derivatives - Approximately 60mg per day orally: 40mg per day Beta-Carotene/β-Carotene, 10mg per day ATRA and 10mg per day Axerophthol palmitate);

- All-Trans-Retinoic Acid (ATRA - analogues and/or derivatives) - In vitro, review and in vivo publications;

- Solution of retinoids in vitamin E in the Di Bella Method biological multitherapy;

- The Di Bella Method (A Fixed Part - Alpha tocopheryl acetate/Vitamin E, approximately 20 grams per day orally);

- Cancer and Vitamin E (analogues and/or derivatives) and cancer - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- The Di Bella Method (A Fixed Part - Calcium, 2 grams per day, orally);

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

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- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis;

- Neuroblastoma: Complete objective response to biological treatment;

- Oesophageal squamocellular carcinoma: a complete and objective response;

- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;

- The Di Bella Method Increases by the 30% the survival rate for Pancreas tumors and for this reason should be proposed as first line therapy for this type of cancer;

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide.