Genetic Polymorphisms of Long Non-coding RNA Linc00312 Are Associated With Susceptibility and Predict Poor Survival of Nasopharyngeal Carcinoma

Zhen Guo; Mei-Hua Bao; Yun-Xia Fan; Yan Zhang; Hai-Yan Liu; Xiao-Long Zhou; Ben Wu; Qing-Qing Lu; Bin-Sheng He; Xu-Ying Nan; Jiao-Yang Lu

doi:10.3389/fcell.2021.698558

Genetic Polymorphisms of Long Non-coding RNA Linc00312 Are Associated With Susceptibility and Predict Poor Survival of Nasopharyngeal Carcinoma

Front Cell Dev Biol. 2021 Jul 16:9:698558. doi: 10.3389/fcell.2021.698558. eCollection 2021.

Authors

Zhen Guo^{1

2}, Mei-Hua Bao^{1

2}, Yun-Xia Fan^{1

2}, Yan Zhang^{1

2}, Hai-Yan Liu^{1

2}, Xiao-Long Zhou^{1

2}, Ben Wu^{1

2}, Qing-Qing Lu³, Bin-Sheng He^{1

2}, Xu-Ying Nan^{1

4}, Jiao-Yang Lu^{1

2}

Affiliations

¹ Academician Workstation, Changsha Medical University, Changsha, China.
² Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, China.
³ Geneis Beijing Co., Ltd., Beijing, China.
⁴ School of Chemistry and Chemical Engineering, Hainan Normal University, Haikou, China.

Abstract

Background: Linc00312 is dysregulated in nasopharyngeal carcinoma (NPC) and participates in the initiation and progression of NPC. Our previous studies suggested that linc00312 was able to enhance the sensitivity of NPC cells to irradiation and NPC patients with higher expression of linc00312 was associated with better short-term curative effect and overall survival. The single nucleotide polymorphisms (SNPs) of lncRNAs may influence the disease course and outcome by affecting the expression, secondary structure or function of lncRNAs. However, the role of SNPs in linc00312 on the occurrence and survival of NPC remains unknown.

Methods: We recruited 684 NPC patients and 823 healthy controls to evaluate the association between linc00312 SNPs and NPC susceptibility by using multivariate logistic regression analysis. Kaplan-Meier analysis and Cox proportional hazards regression were applied to assess the effect of linc00312 SNPs on the survival of NPC patients. The relative expression of linc00312 in NPC tissues was determined by real-time PCR. The interaction between linc00312 and mir-411-3p was explored by luciferase reporter assay. In silico prediction of the changes on linc00312 folding structure was conducted by RNAfold WebServer.

Result: We demonstrated that rs12497104 (G > A) GA genotype carriers had a higher risk than others for suffering from NPC (GA vs GG, OR = 1.437, P = 0.003). Besides, patients with rs12497104 AA genotype showed a poorer overall survival in contrast to GG genotype (AA vs GG, HR = 2.117, P = 0.011). In addition, the heterozygous carriers of rs15734 (G > A) and rs164966 (A > G) were correlated with decreased risk of NPC (GA vs GG, OR = 0.778, P = 0.031; GA vs AA, OR = 0.781, P = 0.033, respectively). We found that the three SNPs might influence the expression of linc00312 in a genotype specific feature. The local centroid secondary structure as well as the minimum free energy of linc00312 were changed following the candidate SNPs alterations. Besides, we revealed that the G to A alteration at rs12497104 disrupted the binding between mir-411-3p and linc00312.

Conclusion: Our results indicated genetic polymorphisms of linc00312 might serve as potential biomarkers for NPC carcinogenesis and prognosis.

Keywords: linc00312; nasopharyngeal carcinoma; polymorphism; survival; susceptibility.