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Overexpression of the lncRNA FER1L4 inhibits paclitaxel tolerance of ovarian cancer cells via the regulation of the MAPK signaling pathway
Author(s) -
Liu Siwei,
Zou Bingyu,
Tian Tian,
Luo Xiaohui,
Mao Banyun,
Zhang Xun,
Lei Huajiang
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28032
Subject(s) - biology , paclitaxel , ovarian cancer , cancer research , cell growth , downregulation and upregulation , cell culture , apoptosis , cell cycle , mapk/erk pathway , flow cytometry , cancer , immunology , signal transduction , microbiology and biotechnology , genetics , gene
To determine how the lncRNA FER1L4 in ovarian cancer cells influences paclitaxel (PTX) resistance, we examined the expression level of FER1L4 in human ovarian epithelial cell lines IOSE80 and HOSEpiC and human ovarian cancer cell lines OVCAR‐3, Caov‐3, and SKOV3 through RNA isolation and quantitative polymerase chain reaction (qRT‐PCR). SKOV3 cell lines were treated with PTX. The cell survival rate and apoptosis rate of SKOV3 and SKOV3‐PR at different PTX dose levels were evaluated. Next, qRT‐PCR was performed to detect the expression of FER1L4 in SKOV3 and SKOV3‐PR cell lines. SKOV3‐PR cell lines were transfected with pcDNA3.1 as the control group (SKOV3‐PR/pcDNA3.1) or pcDNA3.1‐FER1L4 to upregulate the expression level of FER1L4 (SKOV3‐PR/pcDNA3.1‐FER1L4). The level of cell survival, apoptosis, and colony formation were compared between the two groups using MTT, flow cytometry analysis, and colony formation assay. To reveal the molecular mechanism, we measured the relative protein phosphorylation level of ERK and MAPK in SKOV3, SKOV3‐PR, SKOV3‐PR/pcDNA3.1, and SKOV3‐PR/pcDNA3.1‐FER1L4 groups using an enzyme‐linked immunosorbent assay. The effects of SB203580 (a p38 MAPK inhibitor) on PTX were also investigated to reveal the function of the MAPK pathway on the PTX tolerance of SKOV3. In comparison with normal ovarian epithelial cells, FER1L4 was downregulated. The FER1L4 level was decreased in human ovarian cancer cells with drug resistance than in common ovarian cancer cells. The upregulation of FER1L4 could promote the PTX sensitivity of ovarian cancer cells. The increased level of FER1L4 could suppress the PTX resistance of ovarian cancer cells through the inhibition of the MAPK signaling pathway.