circAGFG1 sponges miR-28-5p to promote non-small-cell lung cancer progression through modulating HIF-1α level

Abstract

Circular RNAs (circRNAs) have gained much attention for their crucial regulatory roles in human diseases and cancers. However, the role and the mechanism of circRNA ArfGAP with FG repeats 1 (circAGFG1) in non-small-cell lung cancer (NSCLC) are still largely unknown. circAGFG1 was highly expressed in NSCLC, and high expression of circAGFG1 was closely related to the low survival rate of NSCLC patients. circAGFG1 knockdown inhibited the proliferation, migration, and invasion and promoted the apoptosis of NSCLC cells. circAGFG1 bound to miR-28-5p in NSCLC cells, and circAGFG1 promoted NSCLC progression partly through sponging miR-28-5p in vitro. HIF-1α was a target of miR-28-5p, and miR-28-5p overexpression-mediated influences in NSCLC cells were partly overturned by the addition of HIF-1α overexpression plasmid. circAGFG1/miR-28-5p/HIF-1α axis regulated cellular glycolytic metabolism in NSCLC cells. circAGFG1 silencing restrained the xenograft tumor growth in vivo. circAGFG1 promoted the proliferation, migration, and invasion and suppressed the apoptosis of NSCLC cells through accelerating the glycolysis via miR-28-5p/HIF-1α axis.

Long Noncoding RNAs and Circular RNAs in the Metabolic Reprogramming of Lung Cancer: Functions, Mechanisms, and Clinical Potential

“…Experimentally, circAGFG1 enhanced the malignant behaviors of NSCLC cells by targeting miR-28-5p, with the latter interacting with the 3 untranslated region (3UTR) of HIF-1 α . Additionally, the enhanced circAGFG1/miR-28-5p/HIF-1 α axis could subsequently upregulate the expression of key proteins (GLUT1, PGK1, and PKM2) involved in aerobic glycolysis and promote glucose consumption, lactate production, and ATP levels in A549 cells [ 29 ].…”

“…The lncRNAs include DUXAP8, IGFBP4-1, BCYRN1, CRYBG3, LINC00243, AC020978, LINC01123, HOXA11-AS, ABHD11-AS1, AL355338, HOTAIRM1, CTD-2245E15.3, CCAT1, MINCR, and PVT1-5 [ 22 , 23 , 25 , 26 , 28 , 31 , 33 – 37 , 49 – 51 , 53 ]. The circRNAs comprise circMYLK, circMAGI3, circAGFG1, circSLC25A16, circ-MEMO1, circDCUN1D4, circ-ERBB2, circTADA2A, circ-PGC, circPUM1, circ_0000517, circ-PITX1, circ_0006677, circNFIX, circ-ENO1, circ-LDLRAD3, and circ_0003028 [ 20 , 24 , 29 , 30 , 32 , 39 – 48 , 52 , 55 ]. In fact, some of them were also shown to have potential as prognostic indicators in patients with LC; they included DUXAP8, LINC00243, AC020978, LINC01123, HOXA11-AS, ABHD11-AS1, AL355338, circMYLK, circMAGI3, circAGFG1, circSLC25A16, circ-MEMO1, circDCUN1D4, circ-PGC, circPUM1, circ_0000517, circ_0006677, circNFIX, CCAT1, and MINCR [ 20 , 22 , 24 , 26 , 29 – 36 , 39 , 42 – 44 , 46 , 47 , 50 , 53 ].…”

“…The circRNAs comprise circMYLK, circMAGI3, circAGFG1, circSLC25A16, circ-MEMO1, circDCUN1D4, circ-ERBB2, circTADA2A, circ-PGC, circPUM1, circ_0000517, circ-PITX1, circ_0006677, circNFIX, circ-ENO1, circ-LDLRAD3, and circ_0003028 [ 20 , 24 , 29 , 30 , 32 , 39 – 48 , 52 , 55 ]. In fact, some of them were also shown to have potential as prognostic indicators in patients with LC; they included DUXAP8, LINC00243, AC020978, LINC01123, HOXA11-AS, ABHD11-AS1, AL355338, circMYLK, circMAGI3, circAGFG1, circSLC25A16, circ-MEMO1, circDCUN1D4, circ-PGC, circPUM1, circ_0000517, circ_0006677, circNFIX, CCAT1, and MINCR [ 20 , 22 , 24 , 26 , 29 – 36 , 39 , 42 – 44 , 46 , 47 , 50 , 53 ]. Besides, two other lncRNAs, LINC01537 and ARHGAP10, were only found to have potential as prognostic indicators [ 19 , 38 ].…”

“…It is worth noting that in contrast to other “bad” ncRNAs discussed in this review, the expression of the three in LC was all observed to positively correlate with better survival outcomes of the patients [ 38 , 39 , 46 ]. Although LC tissue was the sample type detected in majority of the researches included in the review, two circRNAs, circ_0008928 and circAGFG1, were reported to be deregulated in the serum of LC patients, which make them potential noninvasive circulating biomarkers for LC diagnosis or prognosis [ 21 , 29 ]. circ_0008928 was found to be significantly overexpressed in serum exosomes of patients with cisplatin-resistant NSCLC compared to those with cisplatin-sensitive NSCLC, making it a potential diagnostic biomarker in cisplatin-resistant NSCLC [ 21 ].…”

“…circ_0008928 was found to be significantly overexpressed in serum exosomes of patients with cisplatin-resistant NSCLC compared to those with cisplatin-sensitive NSCLC, making it a potential diagnostic biomarker in cisplatin-resistant NSCLC [ 21 ]. Besides, circAGFG1 expression was found to be greatly upregulated in both serum samples and LC tissues of patients with NSCLC; also, it was confirmed to be a potential diagnostic and prognostic biomarker for poor survival outcomes [ 29 ].…”