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

Abstract

PURPOSE:

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.

• Authors: Xuemin Wei, Yuehua Zhou, Jin Qiu, Xiaojie Wang, Yan Xia, Long Sui
• Journal: Journal of B.U.ON. : official journal of the Balkan Union of Oncology (J BUON) 2019 May-Jun Vol. 24 Issue 3 Pg. 1020-1026 ISSN: 2241-6293 [Electronic] Cyprus
• PMID: 31424656 (Publication Type: Journal Article)

Chemical References

• RNA, Long Noncoding
• TUG1 long noncoding RNA, human
• Cisplatin

Topics

• Cell Line, Tumor
• Cisplatin (pharmacology)
• Female
• HeLa Cells
• Humans
• MAP Kinase Signaling System
• RNA, Long Noncoding (metabolism)
• Transfection
• Uterine Cervical Neoplasms (drug therapy, metabolism)