HnRNP-L-regulated circCSPP1/miR-520h/EGR1 axis modulates autophagy and promotes progression in prostate cancer

Abstract

The circRNAs, a new subclass of non-coding RNAs that are catalyzed by RNA-binding proteins (RBPs), have been reported to be associated with the progression of multiple types of cancer. We previously discovered that heterogeneous nuclear ribonucleoprotein L (HnRNP-L), a multi-functional RBP, is associated with pro-proliferation and anti-apoptosis activities in prostate tumor cells. In this study, we aim to establish the biological relevance of circCSPP1 (a newly discovered signature circRNA in prostate cancer [PCa]) and HnRNP-L to prostate cancer progression. First, we demonstrated that circCSPP1 expression was higher in prostate cancer tissues than in benign tissues and higher in prostate cancer cells than in benign cells. Then, the in vitro gain- and loss-of-function experiments showed that the circCSPP1 expression in prostate cancer cells was regulated by HnRNP-L, and the increased circCSPP1 significantly induced autophagy, which led to an enhanced potential in proliferation, migration, and invasion of prostate cancer cells. These results were consistent with the in vivo experiment where increased or decreased circCSPP1 was associated with higher or slower growth rate in grafted tumors. Finally, we demonstrated the potential competing endogenous RNA network, involving circCSPP1, miR-520h, and early growth response factor 1 ( EGR1 ), in prostate cancer cells, which may play an important role in prostate cancer progression. Our study indicated that the increase in circCSPP1 in prostate cancer, which may be catalyzed by HnRNP-L, can induce cellular autophagy through the circCSPP1-miR-520h- EGR1 axis, leading to the progression of prostate tumor. This newly discovered circRNA biomarker may be used for clinical prognosis of prostate cancer as well as for development of novel therapy plans.

Circular RNA circCSPP1 promotes the occurrence and development of colon cancer by sponging miR-431 and regulating ROCK1 and ZEB1

“…The upregulated expression and the stability of circCSPP1 render it a potential biomarker and a diagnostic and therapeutic target in human cancers. CircCSPP1 was previous to be upregulated in liver cancer [ 30 ], prostate cancer [ 31 ], ovarian cancer [ 32 ]and glioma cancer [ 33 ]. In addition, circCSPP1 sponges different miRNAs including miR-520 h, miR-378 and miR-1182 to regulate tumor progression in these studies.…”

The emerging roles of circular RNA-mediated autophagy in tumorigenesis and cancer progression

“…Early growth response factor 1 (EGR1) was identified as a transcriptional regulator of autophagy, modulating the expression of autophagy-related genes [ 76 ]. CircCSPP1 facilitates autophagy and enhances the progression of prostate cancer (PCa), via the miR-520h/EGR1 axis [ 77 ]. Insulin-like growth factor 2 receptor (IGF2R) also regulates the autophagic processes.…”

miR‑let‑7c‑3p targeting on Egr‑1 contributes to the committed differentiation of leukemia cells into monocyte/macrophages

“…However, when the cell is stimulated by some physical and chemical factors, the rapid activation of Egr-1 allows cells to enter the proliferation phase from the resting phase, which in turn leads to cell proliferation (22,23). In tumor cells, the role of Egr-1 is more complex and can be expressed as an oncogene or tumor suppressor gene in different types of tumor, for example, Egr-1 promotes the malignant behaviors of LC cells (24), circCSPP1-miR-520h-Egr-1 activation axis lead to the progression of prostate tumor (25), and Egr-1 as a potential oncogene that promotes cell proliferation and defines Egr-1 as a new molecular target in DLBCL non-Hodgkin lymphomar (26). As far as proliferation and differentiation of leukemia cells are concerned, although there are some studies associating it with the inhibition of proliferation and induction of differentiation of leukemia cells (27,28), its role in the committed differentiation of leukemia cells into monocyte/macrophages is rarely reported.…”