Effects of lncRNA ANRIL‑knockdown on the proliferation, apoptosis and cell cycle of gastric cancer cells

Abstract

Gastric cancer is one of the most common types of malignant tumor of the gastrointestinal tract worldwide. Cisplatin (DDP) is a commonly used chemotherapeutic drug in the clinic; however, the resistance of gastric cancer cells to DDP limits its efficacy. In the present study, drug-resistant gastric cancer cell lines were constructed using the stepwise continuous selection method, and the relative expression levels of long non-coding RNA (lncRNA) CDKN2B antisense RNA 1 (ANRIL) and microRNA (miR)-181a-5p were detected using reverse transcription-quantitative PCR. The knockdown of lncRNA ANRIL and miR-181a-5p expression was performed by transfection with shRNA-ANRIL and an miR-181a-5p inhibitor, respectively. Cellular proliferation and sensitivity to DDP were assessed using Cell Counting Kit-8 analysis. Cell apoptosis and cell cycle distribution were assessed using flow cytometry and western blotting. The binding relationships between ANRIL, miR-181a-5p and cyclin G1 (CCNG1) were verified using a dual luciferase reporter assay. The results revealed that the expression levels of miR-181a-5p were downregulated in all drug-resistant cell lines. ANRIL-knockdown inhibited cellular proliferation, and promoted apoptosis and cell cycle arrest; however, following the knockdown of miR-181a-5p, the inhibition of cell cycle arrest was alleviated. Notably, miR-181a-5p, ANRIL and CCNG1 were found to have targeting relationships. In conclusion, the findings of the present study suggested that knocking down the expression of ANRIL inhibited cellular proliferation, and promoted apoptosis and cell cycle arrest. Furthermore, its downstream target, miR-181a-5p, inhibited the proliferation of drug-resistant cells and enhanced their sensitivity to DDP.

Introducing Circulating Vasculature-Related Transcripts as Biomarkers in Coronary Artery Disease

“…Considering the analysis of cellular components and molecular function of the studied transcripts, it indicated their confinement to components and molecules mediating and executing cell proliferation, namely CDK4/6 cyclindependent protein kinase holoenzyme complex mediating RNA polymerase II CTD heptapeptide repeat kinase activity, mediator complex which interacts with and transmits signals from transcription factors to RNA polymerase II, cyclin binding and formation of cyclin D2-CDK4 complex arbitrating serine/threonine kinase activity, which phosphorylates and inactivates RBp, which is also supported by previous results [68,[96][97][98].…”

Role of miR‑181a‑5p in cancer (Review)

“…In BC cell lines HS578T, miR-181a-5p induces autophagy to promote apoptosis and inhibit proliferation by suppressing VDR, thus increasing the sensitivity of cisplatin (173). Similarly, other studies have also demonstrated that miR-181a-5p can induce apoptosis and promote the sensitivity of cisplatin in NSCLC (174), GC (175) and esophageal cancer (61). In additon, these in vitro results were confirmed in vivo.…”

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

“…Six lncRNAs are implicated in the multidrug resistance of gastric cancer cells and facilitate the invasion and metastasis of these drug-resistant cells. They are PVT1 [ 88 , 89 , 90 ], ANRIL [ 34 , 35 ], MALAT1 [ 76 , 77 , 78 , 79 , 80 , 81 ], ZFAS1 [ 101 ], SUMO1P3 [ 95 ], D63785 [ 46 ], and SNHG1 [ 107 ], which mediate the invasion and metastasis of taxane-resistant GC cell lines through the upregulation of their own expression. LEIGC [ 70 ] and HNF1A-AS1 [ 59 ] are also vital in promoting the invasion and metastasis of fluorouracil-resistant GC cell lines.…”

“…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. In addition, 11 lncRNAs have been found to regulate multidrug resistance of GC, these lncRNAs are PVT1 [ 88 , 89 , 90 ], UCA1 [ 97 , 98 , 99 , 100 ], ANRIL [ 34 , 35 ], MALAT1 [ 76 , 78 , 79 , 80 , 81 , 118 ], PANDAR [ 86 ], ZFAS1 [ 101 ], ARHGAP5-AS [ 36 ], HCP5 [ 55 , 56 , 57 ], FEZF1-AS1 [ 49 ], SNHG12 [ 94 ], and SUMO1P3 [ 95 ]. In Adriamycin-resistant GC cells, NEAT1 can promote cell proliferation [ 84 ], and MVIH can also promote the proliferation of gemcitabine-resistant GC cell lines [ 83 ].…”