School of Biological Sciences, National Institute of Science Education and Research, Bhubaneswar, India.
Homi Bhabha National Institute, Mumbai, India.
DNA Cell Biol. 2021 May;40(5):706-712. doi: 10.1089/dna.2021.0056. Epub 2021 Mar 10.
Serine protease inhibitor b5 (SERPINB5) is a tumor suppressor gene that plays a critical role in various cellular processes. In gallbladder cancer (GBC), SERPINB5's aberrant expression is reported but its role in genetic predisposition is not known. We enrolled 270 cases and 296 controls and genotyped them for single nucleotide polymorphisms (SNPs) using direct DNA sequencing, followed by genotype-phenotype analysis in GBC and other cancer cell lines. Luciferase assay was done to determine the role of rs2289521 SNP on expression regulation. We found that two SERPINB5 variants rs2289519 and rs2289521 are significantly associated with GBC and contribute to genetic predisposition. The TT genotype of variant rs2289519 was found to be significantly associated ( = 0.008) with GBC in a recessive model. C allele of rs2289521 increased the risk for GBC significantly at genotypic (CT, = 0.026) and allelic ( = 0.04) levels. analysis and luciferase assay uncovered the probable regulatory role of the rs2289521 variant on expression. Genotype-phenotype correlation in GBC and breast cancer cell lines showed reduced expression of SERPINB5 in the presence of C allele that was consistent with the result of luciferase assay. Overall, our study reveals the genetic association of two SERPINB5 variants with GBC and rs2289521's possible role in the regulation of expression.
丝氨酸蛋白酶抑制剂 B5（SERPINB5）是一种肿瘤抑制基因，在各种细胞过程中发挥着关键作用。在胆囊癌（GBC）中，报道了 SERPINB5 的异常表达，但它在遗传易感性中的作用尚不清楚。我们招募了 270 例病例和 296 例对照，并使用直接 DNA 测序对它们进行单核苷酸多态性（SNP）基因分型，然后在 GBC 和其他癌细胞系中进行基因型-表型分析。进行了荧光素酶测定以确定 rs2289521 SNP 对表达调控的作用。我们发现，SERPINB5 的两个变体 rs2289519 和 rs2289521 与 GBC 显著相关，并有助于遗传易感性。变体 rs2289519 的 TT 基因型在隐性模型中与 GBC 显著相关（=0.008）。rs2289521 的 C 等位基因在基因型（CT，=0.026）和等位基因（=0.04）水平上显著增加了 GBC 的风险。 分析和荧光素酶测定揭示了 rs2289521 变体对表达的可能调节作用。GBC 和乳腺癌细胞系中的基因型-表型相关性表明，在存在 C 等位基因的情况下，SERPINB5 的表达降低，这与荧光素酶测定的结果一致。总体而言，我们的研究揭示了两个 SERPINB5 变体与 GBC 的遗传关联，以及 rs2289521 在表达调控中的可能作用。
