Long non‐coding RNA MIF‐AS1 promotes gastric cancer cell proliferation and reduces apoptosis to upregulate NDUFA4

Abstract

Long non‐coding RNA MIF‐AS1 (lncMIF‐AS1) 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 lncMIF‐AS1‐based signal transduction pathway in mediating the proliferation and apoptosis of gastric cancer cells. Differentially expressed lncRNAs and mRNAs were screened out using microarray analysis, based on the published data (GSE63288), and validated using quantitative RT‐PCR. Target relationships between lncRNA‐micro RNA (miRNA) and miRNA‐mRNA were predicted by bioinformatics analysis and verified by dual‐luciferase reporter assay. Protein expression of NDUFA4, COX6C and COX5B 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 lncMIF‐AS1 and NDUFA4 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 miRNA linker between lncMIF‐AS1 and NDUFA4, which was negatively regulated by lncMIF‐AS1 and its depletion is the main cause of NDUFA4 overexpression (P < .01). The upregulated expression of NDUFA4 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 lncMIF‐AS1/miR‐212‐5p/NDUFA4 signal transduction may provide a promising therapeutic target for the treatment of gastric cancer.

Identification of the complex regulatory relationships related to gastric cancer from lncRNA‐miRNA‐mRNA network

“…[5][6][7] In addition, studies have found that some aberrant regulations between microRNA (miRNA) and mRNA have an important impact on the progression of gastric cancer. For the abnormal regulations between long noncoding RNA (lncRNA) and messenger RNA (mRNA), some studies have shown that lncRNA can promote the proliferation and metastasis of gastric cancer cells by regulating the differentially expressed mRNA.…”

“…For the abnormal regulations between long noncoding RNA (lncRNA) and messenger RNA (mRNA), some studies have shown that lncRNA can promote the proliferation and metastasis of gastric cancer cells by regulating the differentially expressed mRNA. [5][6][7] In addition, studies have found that some aberrant regulations between microRNA (miRNA) and mRNA have an important impact on the progression of gastric cancer. 2,4,8 For the relationships of lncRNA-miRNA, although lncRNA and miRNA do not have the function of encoding proteins, the mutual regulations between lncRNA and miRNA can lead to abnormal expression of some signaling pathways and have an important influence on the growth, metastasis, metabolism, and apoptosis of gastric cancer cells.…”

The functions and targets of miR‐212 as a potential biomarker of cancer diagnosis and therapy

“…One study found that miR‐212‐5p may induce degradation or inhibit the expression of NDUFA4. Moreover, LncMIF‐AS1 was found to promote the expression of NDUFA4 in GC cells by binding miR‐212‐5p, and the recovered NDUFA4 strengthened the proliferative ability and prevented apoptosis of GC cells in vitro …”

“…Moreover, LncMIF-AS1 was found to promote the expression of NDUFA4 in GC cells by binding miR-212-5p, and the recovered NDUFA4 strengthened the proliferative ability and prevented apoptosis of GC cells in vitro. 31…”

Long Non-coding RNAs Involved in Metabolic Alterations in Breast and Prostate Cancers

“…In silico analysis speculates that SNHG3 can function by sponging miR-186-5p. In gastric cancer tissues, expression levels of lncRNA MIF-AS1 ( lncMIF-AS1 ) and complex IV subunit NADH dehydrogenase1 alpha subcomplex 4 (NDUFA4) are higher compared with those in non-cancerous tissues ( 72 ). Mechanistically, lncMIF-AS1 sponges miR-212-5p to activate NDUFA4 expression.…”