Prognostic value of LncRNA PSMA3-AS1 in prostate cancer and its potential regulatory mechanism

Abstract

Objective: Prostate adenocarcinoma (PRAD) is asymptomatic in the early stages and most patients are diagnosed at an advanced stage, which leads to a poor prognosis. Therefore, an effective prognostic marker is required to improve PRAD prognosis.

Methods: A total of 128 patients with PRAD were included in the study. PSMA3-AS1 and miR-29a-3p expression in tissues was detected using RT-qPCR. CCK-8 and Transwell assays were then used to evaluate the proliferative, migratory, and invasive capacities of prostate cancer cell lines. A DLR assay confirmed the binding relationship between PSMA3-AS1 and miR-29a-3p. The five-year prognosis of PRAD patients was analyzed using a Kaplan-Meier plotter curve.

Results: PSMA3-AS1 was highly expressed in PRAD tissues, and patients with high expression had poor 5-year survival. In contrast, miR-29a-3p was poorly expressed in PRAD tissues. PSMA3-AS1 bound to miR-29a-3p in a targeted manner and the levels showed a negative correlation. Knocking down PSMA3-AS1 could increase the level of miR-29a-3p and slow the proliferation of PRAD cell lines, as well as inhibiting their migration and invasion ability.

Conclusion: A high level of PSMA3-AS1 was strongly linked to a poor prognosis for patients and is expected to serve as a prognostic marker for PRAD. Furthermore, PSMA3-AS1 knockdown increased the level of miR-29a-3p and reduced the physiological activity of cancer cells. Therefore, regulating the expression of the PSMA3-AS1/miR-29a-3p axis could influence PRAD development.

Keywords: PSMA3-AS1; Prognostic; Prostate adenocarcinoma; miR-29a-3p.

Fig. 1

PSMA3-AS1 expression and its prognostic value. Database analysis revealed that PSMA3-AS1 was highly expressed in PRAD cancer tissues (A). Our RT-qPCR also revealed that PSMA3-AS1 was notably upregulated in PRAD cancer tissues (B). In addition, the Kaplan Meier curve results showed that patients in the PSMA3-AS1 high expression group had shorter 5-year prognostic survival (C), (** P < 0.01 vs. normal)

Fig. 2

PSMA3-AS1 levels in PRAD cell lines. PSMA3-AS1 levels were significantly elevated in PRAD cell lines (A). Knockdown of PSMA3-AS1 resulted in significantly lower PSMA3-AS1 expression levels in prostate cancer cell lines (B), (** P < 0.01 vs. RWPE-1 or control)

Fig. 3

Effect of PSMA3-AS1 expression on PRAD cell lines. Knockdown of PSMA3-AS1 resulted in a significant reduction in the proliferative capacity of PRAD cell lines (A and B). Knockdown of PSMA3-AS1 resulted in a significant reduction in the migration and invasion ability of PRAD cell lines (C-F), (** P < 0.01 vs. control)

Fig. 4

Targeted binding of PSMA3-AS1 to miR-29a-3p. Possible binding sites of PSMA3-AS1 and miR-29a-3p (A). DLR experiments verified the binding relationship between PSMA3-AS1 and miR-29a-3p (B-C). PSMA3-AS1 was negatively correlated with miR-29a-3p expression level (D). In PRAD cancer tissues, miR-29a-3p was significantly reduced (E), (** P < 0.01 vs. mimic NC or normal; ## P < 0.01 vs. inhibitor NC)

Fig. 5

MiR-29a-3p expression level in PRAD cell lines. The miR-29a-3p expression level was significantly decreased in all PRAD cell lines (A). In PRAD cell lines, knockdown of PSMA3-AS1 caused a significant increase in miR-29a-3p level; however, this effect was notably suppressed by the addition of miR-29a-3p inhibitor (B-C), (** P < 0.01 vs. sh-NC; ## P < 0.01 vs. sh- PSMA3-AS1 + inhibitor NC)

Fig. 6

Effect of miR-29a-3p levels on PRAD cell lines. Inhibition of miR-29a-3p expression also reversed the decrease in proliferation, migration and invasion of LNCaP and PC-3 cells due to reduced PSMA3-AS1 expression levels (A-F), (** P < 0.01 vs. sh-NC; ## P < 0.01 vs. sh- PSMA3-AS1 + inhibitor NC)