LncRNA UCA1 acts as a sponge of miR-204 to up-regulate CXCR4 expression and promote prostate cancer progression

Abstract

Prostate cancer (PCa) is a devastating malignant disease with a poor prognosis. The aim of current study is to investigate the role of lncRNA-urothelial carcinoma associated 1 (UCA1) in the progression of PCa. We evaluated the expression levels of UCA1 in a total of 16 benign prostatic hyperplasia tissues (BPH) and 40 PCa tissues, as well as PCa cells. The functional regulatory effects of UCA1 were investigated using a series of cell function approaches. Our data showed that UCA1 is frequently overexpressed in PCa tissues compared with BPH tissues (P<0.01). Moreover, the higher expression of UCA1 was observed in patients with Gleason score ≥8 (P<0.05). In consistent, we found the expression levels of UCA1 was higher in the PCa cell lines PC-3, LnCaP, and DU-145 than in the normal prostate epithelial cell line RWPE-1 (P<0.01). Functionally, we found knockdown of UCA1 in PC-3 significantly suppressed cell growth and invasion of PC-3, while overexpression of UCA1 in DU-145 cells promote cell growth and invasion. Mechanistically, UCA1 overexpression permitted activation of CXCR4 oncogenes through inhibition of miR-204 activity, as evidenced by the positive association of these two genes with UCA1 levels and inverse correlation with miR-204 expression in PCa tissues. Luciferase activity assay further confirmed the targetting relationship between UCA1 and miR-204, CXCR4, and miR-204. The up-regulation of UCA1 in PC-3 cells significantly impaired the inhibitory effect of miR-204 on CXCR4 expression. Taken together, our research revealed that UCA1 works as an oncogene by targetting miR-204. The UCA1-miR-204-CXCR4 regulatory network regulated the growth and metastasis of PCa, providing new insight in the management of patients with such malignancy.

Long non-coding RNA UCA1 promotes malignant phenotypes of renal cancer cells by modulating the miR-182-5p/DLL4 axis as a ceRNA

“…UCA1 promotes the progression of melanoma by sponging miR-28-5p [22]. In Prostate cancer, UCA1 works as an oncogene by targeting miR-204 [28]. The above studies are consistent with our research.…”

“…Knockdown of UCA1 decreased DLL4 expression of renal cancer cells in vivo (g). Data were shown as mean ± standard deviation (SD) of those biological replicates or samples (*P < 0.05, **P < 0.01) [28][29][30], and our study is also a good example on the relation furthermore. LncRNAs function as miRNAs sponges or decoys that titrate the concentration of miR-NAs and therefore prevent miRNAs binding specific mRNAs.…”

“…The Long non-coding RNA UCA1 was located in chromosome 9p13.12, and has been found to be overexpressed in tumor tissues, such as esophageal squamous cell carcinoma,colorectal cancer, ovarian cancer, bile duct carcinoma and melanoma etc. [16][17][18][19][20][21][22][23].UCA1 are participated in the tumorigenesis and progression, functioning as an oncogene [24][25][26][27][28][29][30]. However, the relation between UCA1 and renal cancer is still unknown and mysterious particularly.…”

“…Accumulating evidences suggested that long non-coding RNAs (lncRNAs) perform important or vital functions in the malignant tumors [9][10][11][12][13][14][15]. LncRNA urothelial cancer associated 1 (UCA1) is abnormally expressed in esophageal squamous cell carcinoma, colorectal cancer, gastric cancer melanoma cells, pancreatic cancer, thyroid cancer, lung cancer and so on [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. In vitro and in vivo assays were conducted to further explore its underlying roles in tumor progression.…”

LncRNA UCA1 maintains the low‐tumorigenic and nonmetastatic status by stabilizing E‐cadherin in primary prostate cancer cells

“…In bladder cancer cells, LncRNA UCA1 can enhance cell proliferation, metastasis, and drug resistance. [14][15][16][17] It has been reported that UCA1 contributes to the progression of prostate cancer by regulating proliferation and metastasis through inactivation of KLF4-KRT6/13 signaling pathway, 18 and functioning as a sponge for miR-184, 19 miR-204, 20 or miR-498. 21 Moreover, UCA1 promotes progression of colon cancer 22 and osteosarcoma, 23 and correlates with poor prognosis of ovarian cancer patients.…”