口腔鳞状细胞癌中 miR-365 的下游靶标分析揭示了与化疗耐药性的不同关系

Life Pub Date : 2024-06-10 DOI:10.3390/life14060741
Brendon Yu, Nathaniel Kruse, K. Howard, Karl Kingsley
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摘要

众所周知,miR-365 等 microRNA 在包括口腔癌在内的许多肿瘤中表达失调,但人们对它们的作用或功能知之甚少。本项目的目的是评估 miR-365 的下游靶点,以确定任何潜在的途径或影响。对口腔癌细胞系(SCC4、SCC9、SCC15、SCC25 和 CAL27)进行 qPCR 筛选时,使用了 miR-365 的下游靶点(miRdatabase 靶点评分大于 90)。每种口腔癌细胞系都表达了 miR-365 的下游靶标:钼辅助因子合成-2(MOCS2)、促红细胞生成素受体(EPOR)、含 IQ 矩阵-K(IQCK)、羧肽酶 A3(CPA3)、溶质运载家族 24 成员-3(SLC24A3)和含盘旋卷曲结构域 47(CCDC47),但表达水平略有不同。不过,泛素蛋白连接酶 E3 成分 n-recognin-3(UBR3)、nudix hydrolase-12(NUDT12)、锌指 CCHC-type containing-14(ZCCHC14)和同源框和亮氨酸拉链编码(HOMEZ)的表达也有差异。这些数据表明,许多 miR-365 靶点在所筛选的口腔癌中都有表达,其中 UBR3、ZCCHC14、HOMEZ 和 NUDT12 的差异表达可能与两种特定口腔癌细胞系(SCC25 和 SCC9)的化疗耐药性有关。这些结果表明,这种差异表达可能是治疗表现出 miR-365 和化疗耐药性的肿瘤患者的潜在靶点。
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Downstream Target Analysis for miR-365 among Oral Squamous Cell Carcinomas Reveals Differential Associations with Chemoresistance
Expression of microRNAs, such as miR-365, is known to be dysregulated in many tumors, including oral cancers, although little is known about their role or functions. The objective of this project is to evaluate the downstream targets of miR-365 to determine any potential pathways or effects. Downstream targets for miR-365 (miRdatabase target scores >90) were used for qPCR screening of oral cancer cell lines (SCC4, SCC9, SCC15, SCC25, CAL27). Each oral cancer cell line expressed miR-365 downstream targets molybdenum cofactor synthesis-2 (MOCS2), erythropoietin receptor (EPOR), IQ motif containing-K (IQCK), carboxypeptidase A3 (CPA3), solute carrier family 24 member-3 (SLC24A3), and coiled-coil domain containing 47 (CCDC47)—although the expression levels varied somewhat. However, differential results were observed with ubiquitin protein ligase E3 component n-recognin-3 (UBR3), nudix hydrolase-12 (NUDT12), zinc finger CCHC-type containing-14 (ZCCHC14), and homeobox and leucine zipper encoding (HOMEZ). These data suggest that many of the miR-365 targets are expressed in the oral cancers screened, with the differential expression of UBR3, ZCCHC14, HOMEZ, and NUDT12, which may be correlated with chemoresistance among two specific oral cancer cell lines (SCC25, SCC9). These results suggest this differential expression may signal potential targets for patient treatment with tumors exhibiting miR-365 and chemotherapeutic resistance.
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