Low expression of TUG1 promotes cisplatin sensitivity in cervical cancer by activating the MAPK pathway. 2019

Xuemin Wei, and Yuehua Zhou, and Jin Qiu, and Xiaojie Wang, and Yan Xia, and Long Sui
Department of Obstetrics and Gynecology, Tongren Hospital Shanghai Jiaotong University School of Medicine, Shanghai 200336, China.

OBJECTIVE This study aims to investigate whether TUG1 can regulate cisplatin resistance in the disease progression of cervical cancer (CC) by activating the MAPK pathway. METHODS Taurine-upregulated gene 1 (TUG 1) expression in CC tissues and cell lines was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The correlation between TUG1 expression and the prognosis of CC patients was analyzed by Kaplan-Meier method. The regulatory effects of TUG1 on proliferative and apoptotic rates of DDP-induced CC cells were assessed by cell counting kit-8 (CCK-8), colony formation and TUNEL assay, respectively. The target gene of TUG1 was predicted by online bioinformatics. The expression level of the target gene was determined after TUG1 knockdown. Subsequently, proliferative and apoptotic rates of DDP-induced CC cells with knockdown of the target gene were explored as well. By transfection of shRNA TUG1, the protein expressions of Bcl-2, Bax and relative genes in the MAPK pathway were detected by Western blot. RESULTS QRT-PCR showed that TUG1 was highly expressed in CC tissues, especially in those with DDP-resistance. Similarly, TUG1 was highly expressed in CC cell lines as well. Higher expression of TUG1 suggested a worse prognosis of CC patients. TUG1 knockdown inhibited the proliferative rate but accelerated the apoptosis of DDP-induced CC cells. Through bioinformatics prediction, RFX7 was screened out to be the target gene of TUG1. Both mRNA and protein levels of RFX7 were downregulated by TUG1 knockdown. Knockdown of RFX7 could inhibit the proliferative rate and colony formation ability of CC cells. After DDP induction in CC cells, phosphorylated levels of p38 and JNK increased, whereas ERK1/2 expression decreased. CONCLUSIONS TUG1 is highly expressed in CC tissues and closely related with its DDP-resistance. TUG1 knockdown could inhibit the proliferative rate but accelerate the apoptosis of CC cells through activating the MAPK pathway.

UI MeSH Term Description Entries
D002583 Uterine Cervical Neoplasms Tumors or cancer of the UTERINE CERVIX. Cancer of Cervix,Cancer of the Cervix,Cancer of the Uterine Cervix,Cervical Cancer,Cervical Neoplasms,Cervix Cancer,Cervix Neoplasms,Neoplasms, Cervical,Neoplasms, Cervix,Uterine Cervical Cancer,Cancer, Cervical,Cancer, Cervix,Cancer, Uterine Cervical,Cervical Cancer, Uterine,Cervical Cancers,Cervical Neoplasm,Cervical Neoplasm, Uterine,Cervix Neoplasm,Neoplasm, Cervix,Neoplasm, Uterine Cervical,Uterine Cervical Cancers,Uterine Cervical Neoplasm
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D005260 Female Females
D006367 HeLa Cells The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays. Cell, HeLa,Cells, HeLa,HeLa Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014162 Transfection The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES. Transfections
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D062085 RNA, Long Noncoding A class of untranslated RNA molecules that are typically greater than 200 nucleotides in length and do not code for proteins. Members of this class have been found to play roles in transcriptional regulation, post-transcriptional processing, CHROMATIN REMODELING, and in the epigenetic control of chromatin. LincRNA,RNA, Long Untranslated,LINC RNA,LincRNAs,Long Intergenic Non-Protein Coding RNA,Long Non-Coding RNA,Long Non-Protein-Coding RNA,Long Noncoding RNA,Long ncRNA,Long ncRNAs,RNA, Long Non-Translated,lncRNA,Long Intergenic Non Protein Coding RNA,Long Non Coding RNA,Long Non Protein Coding RNA,Long Non-Translated RNA,Long Untranslated RNA,Non-Coding RNA, Long,Non-Protein-Coding RNA, Long,Non-Translated RNA, Long,Noncoding RNA, Long,RNA, Long Non Translated,RNA, Long Non-Coding,RNA, Long Non-Protein-Coding,Untranslated RNA, Long,ncRNA, Long,ncRNAs, Long
D020935 MAP Kinase Signaling System An intracellular signaling system involving the mitogen-activated protein kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade. MAP Kinase Cascade,MAP Kinase Module,MAP Kinase Signaling Cascade,MAP Kinase Signaling Pathway,MAP Kinase Signaling Pathways,ERK Pathway,ERK Signal Tranduction Pathway,ERK1 and ERK2 Pathway,ERK1-2 Pathway,JNK Pathway,JNK Signaling Pathway,MAP Kinase Modules,MAP Kinase Signaling Cascades,MEK-ERK Pathway,p38 Kinase Pathway,p38 Kinase Signaling Pathway,Cascade, MAP Kinase,ERK Pathways,ERK1 2 Pathway,ERK1-2 Pathways,JNK Pathways,JNK Signaling Pathways,Kinase Cascade, MAP,Kinase Pathway, p38,Kinase Pathways, p38,MAP Kinase Cascades,MEK ERK Pathway,MEK-ERK Pathways,Module, MAP Kinase,Pathway, ERK,Pathway, ERK1-2,Pathway, JNK,Pathway, JNK Signaling,Pathway, MEK-ERK,Pathway, p38 Kinase,Pathways, ERK,Pathways, ERK1-2,Pathways, JNK,Pathways, JNK Signaling,Pathways, MEK-ERK,Pathways, p38 Kinase,Signaling Pathway, JNK,Signaling Pathways, JNK,p38 Kinase Pathways

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