Long Non-coding RNA AGAP2-AS1 Silencing Inhibits PDLIM5 Expression Impeding Prostate Cancer Progression via Up-Regulation of MicroRNA-195-5p

Abstract

Prostate cancer remains a significant cause of cancer-related deaths in male population. More recently, accumulating evidence continues to implicate long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in various types of cancers, including prostate cancer. The current study aimed to elucidate the role of lncRNA AGAP2-AS1/miR-195-5p/PDZ and LIM domain 5 (PDLIM5) in prostate cancer progression. Initially, microarray expression profiles were applied to screen differentially expressed lncRNAs/miRNAs/genes associated with prostate cancer. Dual-luciferase reporter and RNA pull-down/RIP assays were subsequently performed to explore the interactions among lncRNA AGAP2-AS1, miR-195-5p, and PDLIM5, after which their expression was detected in cancer tissues and cells. Next, gain-and loss-of-function approaches were employed to elucidate the mechanism of lncRNA AGAP2-AS1/miR-195-5p/PDLIM5 in the processes of cell proliferation, migration and invasion as well as tumor growth. LncRNA AGAP2-AS1 was found to be highly expressed in prostate cancer. Silencing of lncRNA AGAP2-AS1 contributed to the suppression of proliferation, migration and invasion of cancer cells in vitro. Besides, lncRNA AGAP2-AS1 could bind to miR-195-5p which targeted PDLIM5 and subsequently downregulated its expression, ultimately impeding the progression of prostate cancer. Additionally, lncRNA AGAP2-AS1 inhibition led to an up-regulated expression of miR-195-5p and down-regulated PDLIM5 expression, resulting in delayed tumor growth in vivo. Taken together, the key findings of our study demonstrated that lncRNA AGAP2-AS1 silencing exerted suppressive effects on the development of prostate cancer via the miR-195-5pdependent downregulation of PDLIM5. Our findings highlighted the potential of lncRNA AGAP2-AS1 as a promising novel molecular target for prostate cancer therapy.

Genetic susceptibility to prostate cancer in Taiwan: A genome‐wide association study

“…[49][50][51][52] High PDLIM5 expression in tumor tissues correlates with advanced PCa tumors in vivo. 53 We confirmed 35 out of 49 highly significant PCa susceptibility SNPs in Japanese, and 19 of them remained significant after stringent multiple testing adjustment. It appears that Taiwanese have fewer PCa susceptibility loci than Japanese.…”

“…The oncogenic lncRNA AGAP2‐AS1, highly expressed in PCa, promotes PCa by binding to and inhibiting miR‐195‐5p, resulting in the upregulation of PDLIM5 and PCa progression. Silencing AGAP2‐AS1 leads to an upregulation of miR‐195‐5p and subsequent downregulation of PDLIM5 expression, resulting in the suppression of proliferation, migration, and invasion of PCa cells in vitro and the delayed growth of PCa tumors in vivo 53 …”

Exosomal lncRNA HCG18 contributes to cholangiocarcinoma growth and metastasis through mediating miR-424-5p/SOX9 axis through PI3K/AKT pathway

“…lncRNA ZFAS1 was reported to be a diagnosis feature in ESCC tissues [29]. Elevated lncRNA AGAP2-AS1 level was observed in prostate cancer [30]. The role of lncRNA HCG18 was previously reported to be a cancer-promoting gene, related to bladder cancer, papillary thyroid cancer, etc.…”

Identification of Inflammatory Gene in the Congenital Heart Surgery Patients following Cardiopulmonary Bypass via the Way of WGCNA and Machine Learning Algorithms

“…In addition, Xu et al found that PPARGC1B can alleviate IL-1β-mediated osteoarthritis [35]. If PDLIM5 is downregulated, some cancer progression rates will be suppressed [38]. More ceRNAregulated mechanisms need to be further explored and validated.…”