Open AccessAnalysis of lncRNA UCA1‐related downstream pathways and molecules of cisplatin resistance in lung adenocarcinoma
Author(s) -
Zhou Huixin,
Shen Qiang,
Fu Jiali,
Jiang Feng,
Wang Liangxing,
Wang Yumin
Publication year - 2020
Publication title -
journal of clinical laboratory analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 50
eISSN - 1098-2825
pISSN - 0887-8013
DOI - 10.1002/jcla.23312
Subject(s) - txnip , cisplatin , a549 cell , downregulation and upregulation , messenger rna , cancer research , chemistry , microbiology and biotechnology , apoptosis , biology , gene , biochemistry , genetics , chemotherapy , thioredoxin
Background To analyze the lncRNA UCA1‐related downstream pathways and molecules of cisplatin resistance in lung adenocarcinoma. Methods We constructed overexpression and siRNA vectors targeting UCA1 and TXNIP and then used next‐generation sequencing to compare the UCA1 overexpression and negative control from A549 cell. Results It shown that 647 upregulated mRNAs and 633 downregulated differentially expressed mRNAs‐related UCA1, and the top ten upregulated mRNAs were CPD, AC007192.1, TGOLN2, LGR4, TFPI, CYP1B1, TOMM6, HLA‐B, SLC35F6, and TOP2A, and top ten downregulated mRNAs were TXNIP, SESN2, STC2, HSPA1A, MMP10, CHAC1, DNAJB1, AC004922.1, ATF3, and GABARAPL1. We found TXNIP mRNA expression level was the most significantly downexpressed mRNA. TXNIP mRNA expression level of LAD tissues was clearly lower than the adjacent tissues. UCA1 expression level of cisplatin insensitive group was markedly higher than that of cisplatin‐sensitive group, while TXNIP mRNA expression level of cisplatin insensitive group was clearly lower than that of cisplatin‐sensitive group. Compared to the BEAS‐2B, TXNIP mRNA expression level cut down in A549 and A549/DDP cell and that of A549/DDP cell was lower than A549 cell. After UCA1 overexpression, TXNIP mRNA obviously decreased, while proliferation ability and IC50 of A549 heightened. After knocking down UCA1, TXNIP mRNA was significantly increased, while proliferation ability and IC50 of A549/DDP lowered. PPI analysis result showed that TXNIP could interact with multiple proteins such as TXN, DDIT4, and NLRP3. Conclusion UCA1 promoted cisplatin resistance by downregulating TXNIP expression in LAD, and TXNIP could interact with multiple proteins. So, UCA1/TXNIP axis might affect cisplatin resistance in LAD.