FGD5‑AS1 is an oncogenic lncRNA in pancreatic cancer and regulates the Wnt/β‑catenin signaling pathway via miR‑577

Abstract

The objective of the present study was to clarify the expression characteristics of long non-coding RNA (lncRNA) FGD5 antisense RNA 1 (FGD5-AS1) in pancreatic cancer, as well as its biological function and underlying mechanism. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was utilized for the detection of FGD5-AS1 and microRNA (miR)-577 expression levels in pancreatic cancer tissues. Transfection was performed to upregulate or downregulate FGD5-AS1 in pancreatic cancer cell lines. MTT and Transwell assays were then utilized to detect the proliferation, migration and invasion of cancer cells, respectively. Subsequently, dual-luciferase reporter gene assay, RNA immunoprecipitation assay, RNA pull-down assay, RT-qPCR, western blotting, and Pearson's correlation analysis were employed to confirm the regulatory relationships among FGD5-AS1, miR-577, low-density lipoprotein receptor-related protein 6 (LRP6) and β-catenin. Western blotting was employed to determine the expression levels of Axin2, cyclin D1 and c-Myc. The expression level of FGD5-AS1 was upregulated in pancreatic cancer tissues and cell lines. FGD5-AS1 knockdown inhibited pancreatic cancer cell proliferation, migration and invasion. By contrast, miR-577 was significantly inhibited in pancreatic cancer cells and tissues; its downregulation promoted pancreatic cancer cell proliferation, migration and invasion, and reversed the effects of FGD5-AS1 knockdown on pancreatic cancer cells. In addition, it was revealed that miR-577 was a target of FGD5-AS1, and FGD5-AS1 could modulate the expression levels of LRP6, β-catenin, Axin2, cyclin D1 and c-Myc via suppressing miR-577. In conclusion, in pancreatic cancer, highly expressed FGD5-AS1 activated the Wnt/β-catenin signaling and promoted cancer cell proliferation, migration and invasion via suppression of miR-577.

Hypoxia mediates immune escape of pancreatic cancer cells by affecting miR-1275/AXIN2 in natural killer cells

“…miR-1275 downstream target genes were predicted via TargetScan and miRDB online database and screened via Venn diagram to obtain eight intersecting genes ( Figure 6A ). Among them, AXIN2 was previously shown to be highly expressed in a variety of tumors ( 24 , 25 ), including pancreatic cancer ( 26 ), and plays a tumor-promoting role. However, the functions of AXIN2 on NK cells under hypoxic conditions remains vague.…”

Non-coding antisense transcripts: fine regulation of gene expression in cancer

“…Downregulation of FGD5-AS1 led to increased levels of miR-577, resulting in decreased levels of β-catenin and LRP6. This decrease was associated with a reduction in the Wnt signaling pathway and inhibition of cell proliferation, migration and invasion [55] . CERS6-AS1 (ceramide synthase 6 antisense RNA 1) was also identified as being overexpressed in both pancreatic tissue samples and cell lines [56] .…”

“…FGD5-AS1 (FGD5 antisense RNA 1) was shown to be overexpressed in pancreatic cancer and bind to miR-577, which targets β-catenin and LRP6 (low‑density lipoprotein receptor‑related protein 6) [55] . Downregulation of FGD5-AS1 led to increased levels of miR-577, resulting in decreased levels of β-catenin and LRP6.…”

Long noncoding RNAs in pancreas cancer: from biomarkers to therapeutic targets

“…In the same study, it was shown that FGD5-AS1 activates the Wnt/β-catenin signaling pathway by suppressing miR-577, a tumor suppressor in PC. It was reported that the expression of NUTF2P3-001, another lncRNA that increases in cases of hypoxia, plays a positive role in the regulation of KRAS expression and supports cell proliferation in PC [ 39 ].…”