Open AccessLong non‐coding RNA MIF ‐ AS 1 promotes gastric cancer cell proliferation and reduces apoptosis to upregulate NDUFA 4
Author(s) -
Li Linhai,
Li Yuejin,
Huang Yingguang,
Ouyang Yiming,
Zhu Yu,
Wang Yongzhi,
Guo Xiaodong,
Yuan Ying,
Gong Kunmei
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13801
Subject(s) - downregulation and upregulation , cell growth , apoptosis , cancer cell , rna , microbiology and biotechnology , biology , cancer research , flow cytometry , cancer , chemistry , biochemistry , gene , genetics
Long non‐coding RNA MIF ‐ AS 1 (lnc MIF ‐ AS 1) has been found to be upregulated in the tumor tissues of gastric cancer; however, its importance for the progression of gastric cancer remains unknown. Thus, the present study was designed to determine the role of the lnc MIF ‐ AS 1‐based signal transduction pathway in mediating the proliferation and apoptosis of gastric cancer cells. Differentially expressed lnc RNA s and mRNA s were screened out using microarray analysis, based on the published data ( GSE 63288), and validated using quantitative RT ‐ PCR . Target relationships between lnc RNA ‐micro RNA (mi RNA ) and mi RNA ‐ mRNA were predicted by bioinformatics analysis and verified by dual‐luciferase reporter assay. Protein expression of NDUFA 4, COX 6C and COX 5B was detected by western blot. Cell proliferation, cell cycle and apoptosis were determined using colony formation assay and flow cytometry analysis. Oxidative phosphorylation in gastric cancer cells was assessed by levels of oxygen consumption and ATP synthase activity. Expression of lnc MIF ‐ AS 1 and NDUFA 4 were upregulated in gastric cancer tissues and cells as compared with non‐cancerous gastric tissues and cells ( P < .05). MiR‐212‐5p was identified as the most important mi RNA linker between lnc MIF ‐ AS 1 and NDUFA 4, which was negatively regulated by lnc MIF ‐ AS 1 and its depletion is the main cause of NDUFA 4 overexpression ( P < .01). The upregulated expression of NDUFA 4 then greatly promoted the proliferation and decreased the apoptosis of gastric cancer cells through activation of the oxidative phosphorylation pathway. Taken together, the present study implies that inhibition of lnc MIF ‐ AS 1/miR‐212‐5p/ NDUFA 4 signal transduction may provide a promising therapeutic target for the treatment of gastric cancer.