Proteasome 20S subunit alpha 3 antisense RNA 1 (PSMA3-AS1) represents a new cancer-promoting long noncoding RNA in cholangiocarcinoma, as published in Aging. This finding suggests that PSMA3-AS1 could be a target for the treatment of the disease.

It is already known that long noncoding RNAs including PSMA3-AS1 play a crucial role in the development and progression of cancer. However, the role of PSMA3-AS1 in cholangiocarcinoma is not clear.

Here, a team of researchers led by Xingming Jiang from the Second Affiliated Hospital of Harbin Medical University in China examined the expression, function, mechanism, and clinical significance of PSMA3-AS1 in the development of cholangiocarcinoma.


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Using the Cancer Genome Atlas, they found that PSMA3-AS1 was overexpressed in cholangiocarcinoma. This overexpression was related to lymph node invasion, advanced stage, and poor survival.

The researchers also showed that the upregulation of PSMA3-AS1 promoted cholangiocarcinoma cell proliferation, migration, and invasion while its downregulation inhibited these biological processes.

Moreover, PSMA3-AS1 downregulated E-cadherin and upregulated N-cadherin and vimentin thereby promoting epithelial to mesenchymal transition. The transcription factor PAX5 bound to PSMA3-AS1’s promoter region and drove its transcription.

Finally, the researchers showed that PSMA3-AS1 could competitively bind to miR-376a-3p and upregulate laminin subunit gamma 1 (LAMC1), a member of the laminin family, which is involved in basement membrane reestablishment and cancer invasion. This upregulation accelerated the progression of cholangiocarcinoma, the researchers said.  

“This study uncovers that PSMA3-AS1 functions as a cancer-promoting gene in [cholangiocarcinoma], and PAX5/PSMA3-AS1/miR-376a-3p/LAMC1 axis plays a vital role in [cholangiocarcinoma] development,” they concluded.

Reference

Sun D, Li F, Liu L, et al. PSMA3-AS1 induced by transcription factor PAX5 promotes cholangiocarcinoma proliferation, migration and invasion by sponging miR-376a-3p to up-regulate LAMC1. Aging. 2022;12:14(1). doi:10.18632/aging.203828