LncRNA FAM83H-AS1 promotes malignant progression of pancreatic ductal adenocarcinoma by stabilizing FAM83H mRNA to protect β-catenin from degradation

Abstract Background: Pancreatic cancer was prone to metastasis, which leaded to the poor survival and low quality of life. Here, we found that FAM83H-AS1 was highly correlated with metastasis of pancreatic cancer and further explored the functions and mechanisms involving in the malignant progression of pancreatic cancer. Method: We profiled and analyzed the aberrant expression of lncRNA (long non-coding RNA) in TCGA database and screened FAM83H-AS1 most effective in promoting the migration of pancreatic cancer cells. Firstly, the expression level of FAM83H-AS1 in serum, tissues and cells were detected by RT-qPCR, and the distribution of it in pancreatic cancer cells was tested by FISH and nuclear/cytosol fractionation RT-qPCR. Next, a series of functional assays were conducted to elucidate the relationship between FAM83H-AS1 and pancreatic cancer in vivo and vitro. The regulation relationship between FAM83H-AS1 and FAM83H was verified by protein and RNA degradation assays respectively. A series of Co-immunoprecipitation assays was utilized to explore the potential mechanism of FAM83H and β-catenin. Rescue assays were used to illustrate the regulation axis of FAM83H-AS1/FAM83H/ Wnt/β-catenin in pancreatic cancer.Results: FAM83H-AS1 was highly expressed in cancer tissues and serum of PDAC patients, and was correlated with poorer survival. FAM83H-AS1, as an oncogene, promoted the proliferation, invasion and metastasis of PDAC cells by functional assays and bioinformatics analysis. FAM83H, the homologous gene of FAM83H-AS1, also manifested the same biological behaviour as FAM83H-AS1 in PDAC. Also, FAM83H-AS1 protected FAM83H mRNA from degradation and FAM83H directly bound β-catenin. Mechanically, FAM83H-AS1 facilitated the expression of FAM83H by stabilizing its mRNA and promoted FAM83H to decrease the ubiquitylation of β-catenin, which activated the effect genes of Wnt/β-catenin signalling.Conclusions: This study revealed the function of FAM83H-AS1 involving in the progression of PDAC, and might provide a new prognostic indicator and therapy target for PDAC.