MiR-874-3p represses the migration and invasion yet promotes the apoptosis and cisplatin sensitivity via being sponged by long intergenic non-coding RNA 00922 (LINC00922) and targeting Glycerophosphodiester Phosphodiesterase Domain Containing 5 (GDPD5) in gastric cancer cells

Abstract

Our study mainly reports the specific mechanisms of microRNA (miR)-874-3p on drug resistance in gastric cancer (GC). Clinical specimen was collected. The upstream long non-coding RNA (lncRNA) and the downstream gene of miR-874-3p were predicted using bioinformatic analysis with the results being ascertained with dual-luciferase reporter assay. The viability, apoptosis, migration and invasion of transfected GC cells with or without cisplatin (DDP) treatment were evaluated by Cell Counting Kit-8 (CCK-8), flow cytometric, Scratch, and Transwell assays. An animal xenograft model was constructed. Expressions of long intergenic non-coding RNA 00922 (LINC00922), miR-874-3p and potential target genes were quantified by quantitative real-time polymerase-chain reaction (qRT-PCR) and Western blot. MiR-874-3p, which was lower-expressed in drug-resistant GC tissues and cells, was upregulated to repress the viability, migration and invasion but enhance the apoptosis and sensitivity in GC cells with or without DDP resistance. Downregulation of miR-874-3p eliminated the effects of silenced LINC00922, a upstream lncRNA of miR-874-3p, on cell viability, apoptosis, migration and invasion, as well as the expressions of Glycerophosphodiester Phosphodiesterase Domain Containing 5 (GDPD5) and the downstream gene of miR-874-3p in DDP-resistant GC cells. GDPD5 silencing diminished the effects of miR-874-3p downregulation on GDPD5 expression, viability, migration and invasion of DDP-resistant GC cells. Additionally, LINC00922 silencing enhanced the inhibitory effect of DDP on tumor growth, whereas reversing the effects of DDP on LINC00922, miR-874-3p and GDPD5 expressions in tumors. MiR-874-3p, an miRNA, which is sponged by LINC00922 and targets GDPD5, inhibits the GC progression yet enhances the DDP sensitivity in GC.

Long Non-Coding RNAs in Drug Resistance of Gastric Cancer: Complex Mechanisms and Potential Clinical Applications

“…In DDP-resistant GC cell lines, 12 lncRNAs were found to be involved in the regulation and promotion of invasion and metastasis. They are HOTAIR [ 60 , 61 , 62 ], HOTTIP [ 65 ], FAM84B-AS [ 48 ], KLF3-AS1 [ 69 ], SNHG6 [ 93 ], ST7-AS1 [ 106 ], LINC-PINT [ 72 ], and LINC00922 [ 73 ]. Six lncRNAs are implicated in the multidrug resistance of gastric cancer cells and facilitate the invasion and metastasis of these drug-resistant cells.…”

“…For example, in DDP-resistant cell lines, 14 lncRNAs were involved in regulating the proliferation in GC cell lines. These lncRNAs are HOTAIR [ 60 , 61 , 62 , 63 ], HULC [ 66 , 67 ], HOTTIP [ 65 ], DANCR [ 44 ], FAM84B-AS [ 48 ], HMGA1P4 [ 58 ], ASB16-AS1 [ 37 ], KLF3-AS1 [ 69 ], SNHG6 [ 93 ], FOXD1-AS1 [ 37 ], PITPNA-AS1 [ 87 ], ST7-AS1 [ 106 ], LINC-PINT [ 72 ], an LINC00922 [ 73 ]. In 5-FU-, oxaliplatin-, and docetaxel-resistant cell lines, there were five cases (LEIGC [ 70 ], MACC1-AS1 [ 75 ], FGD5-AS1 [ 50 ], HAGLR [ 54 ], and HNF1A-AS1 [ 59 ]), and two cases (lncRNA), respectively, (DUSP5P1 [ 45 ] and SLCO1C1 [ 91 ]), and two lncRNAs (MRUL [ 82 ], D63785 [ 46 ]) were involved in regulating the proliferation of these drug-resistant GC cell lines.…”

Natural products targeting signaling pathways associated with regulated cell death in gastric cancer: Recent advances and perspectives

“…For instance, lncRNA-ncRuPAR was shown to promote apoptosis in human GC cells by inhibiting PAR-1, PI3K/Akt signaling and cyclin D1 (Xu, Yu, et al, 2022b). MiR-874-3p, sponged by LINC00922, was found to inhibit GC progression by targeting glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) and promoting apoptosis (Zhang, Dai, et al, 2022e). CircRNA-ZFR was found to induce cell cycle arrest and promote apoptosis by sponging miR-130a/miR-107 and regulating PTEN signaling in GC cells (Liu et al, 2018).…”