Impact of HOTAIR Gene Polymorphism and Environmental Risk on Oral Cancer

Abstract

Genetic and acquired factors are thought to be interrelated and imperative to estimate the risk and prognosis of oral squamous cell carcinoma (OSCC). HOX transcript antisense intergenic RNA ( HOTAIR) plays crucial roles in gene regulation and is regulated in a variety of cancers. Polymorphisms in HOTAIR have been recently linked to the predisposition to diverse malignancies. In the present study, we aimed to evaluate the influences of HOTAIR gene polymorphisms, combined with environmental triggers, on the susceptibility to oral tumorigenesis. Four single-nucleotide polymorphisms of the HOTAIR gene- rs920778, rs1899663, rs4759314, and rs12427129-were tested in 1,200 control participants and 907 patients with OSCC. We detected a significant association of rs1899663 with the risk of OSCC (adjusted odds ratio, 2.227; 95% confidence interval [95% CI], 1.197 to 4.146; P = 0.012) after adjustment for 3 potential confounders: smoking, betel quid chewing, and alcohol consumption. In further analyses where habitual exposure to each of 3 environmental factors was excluded, we found that, in addition to rs1899663, non-betel quid users who carried the polymorphic allele of rs920778 were more prone to develop OSCC than were those homozygous for wild-type allele (TC: odds ratio [OR], 1.472; 95% CI, 1.069 to 2.029; P = 0.018; TC+CC: OR, 1.448; 95% CI, 1.060 to 1.977; P = 0.020). Moreover, in exploring the relationship between HOTAIR gene polymorphisms and the clinical status of only patients with OSCC who were non-betel quid chewers (excluding the advanced clinical stage), we found that rs920778 and rs4759314 were correlated with the development of large-size tumors (OR, 1.891; 95% CI, 1.027 to 3.484; P = 0.04) and increased lymph node metastasis (OR, 4.140; 95% CI, 1.785 to 9.602; P = 0.001), respectively. Further functional assessments link rs920778 to the regulation of HOTAIR expression and epigenetic status. Our results reveal an interactive effect of HOTAIR gene polymorphisms and betel quid chewing on the development and progression of oral cancer.

Glabridin induces apoptosis and cell cycle arrest in oral cancer cells through the JNK1/2 signaling pathway

“…Oral cancer is a common malignant cancer worldwide and the fifth leading cause of cancer death in Taiwan according to the 2017 annual Statistics of Causes of Death report published by Taiwan's Ministry of Health and Welfare. Conventional treatment of patients with oral cancer includes surgery, chemotherapy and radiotherapy . Despite substantial advances in oral cancer diagnoses and therapies, the prognosis and mortality for patients with oral squamous cell carcinoma remain unfavorable .…”

LncRNA HOTAIR promotes the invasion and metastasis of oral squamous cell carcinoma through metastasis‐associated gene 2

“…The abnormal expression of HOX transcript antisense intergenic RNA (HOTAIR) was first identified in breast cancer tissues, 7 and was continually observed among esophagus, colon, liver, and pancreatic cancers and associated with poor prognosis 8–11 . Notably, HOTAIR was reported to be upregulated in OSCC and HOTAIR gene polymorphism contributed to the risk of oral cancer 12 . HOTAIR, tethering polycomb repressive complex 2 as a scaffold, promoted histone H3 lysine 27 methylation, reprogramed chromatin state, 7 induced epithelial cancer cell into an aggressive pattern, more resembling embryonic fibroblasts and increased cancer invasiveness and metastasis 13 .…”

“…[8][9][10][11] Notably, HOTAIR was reported to be upregulated in OSCC and HOTAIR gene polymorphism contributed to the risk of oral cancer. 12 HOTAIR, tethering polycomb repressive complex 2 as a scaffold, promoted histone H3 lysine 27 methylation, reprogramed chromatin state, 7 induced epithelial cancer cell into an aggressive pattern, more resembling embryonic fibroblasts and increased cancer invasiveness and metastasis. 13 In addition, HOTAIR could decrease the rate of doxorubicin-induced apoptosis and promote autophage in OSCC, whereas interference of HOTAIR could improve cisplatin sensitivity in OSCC.…”

Leptin −2548 G/A polymorphisms are associated to clinical progression of oral cancer and sensitive to oral tumorization in nonsmoking population

“…12,13 The gene of LEP is located on chromosome 7q31. 3 14,15 and the length of its mesenger RNA in adipose tissue is 4.5 kb. 16,17 LEP is also known for its effects on angiogenesis, proinflammatory immune response, hematopoiesis, thrombosis, tumor growth, and metastasis, therefore participates in the regulations of energy balance, adiposity, endocrine systems, immunity, angiogenesis, and oncogenesis.…”