MicroRNA-1205, encoded on chromosome 8q24, targets EGLN3 to induce cell growth and contributes to risk of castration-resistant prostate cancer

Abstract

The chromosome 8q24.21 locus, which contains the proto-oncogene c- MYC , long non-coding RNA PVT1, and microRNAs (miRs), is the most commonly amplified region in human prostate cancer. A long-range interaction of genetic variants with c- MYC or long non-coding PVT1 at this locus contributes to the genetic risk of prostate cancer. At this locus is a cluster of genes for six miRs (miR-1204, −1205, −1206, −1207–3p, −1207–5p, and −1208), but their functional role remains elusive. Here, the copy numbers and expressions of miRs-1204~1208 were investigated using quantitative PCR for prostate cancer cell lines and primary tumors. The data revealed that copy numbers and expression of miR-1205 were increased in both castration-resistant prostate cancer cell lines and in primary tumors. In castration-resistant prostate cancer specimens, the copy number at the miR-1205 locus correlated with expression of miR-1205. Furthermore, functional analysis with an miR-1205 mimic, an miR-1205 inhibitor, and CRISPR/Cas9 knockout revealed that, in human prostate cancer cells, miR-1205 promoted cell proliferation and cell cycle progression and inhibited hydrogen peroxide-induced apoptosis. In these cells, miR-1205 downregulated expression of the Egl-9 family hypoxia inducible factor 3 ( EGLN3 ) gene and targeted a site in its 3’-untranslated region to downregulate its transcriptional activity. Thus, by targeting EGLN3, miR-1205 has an oncogenic role and may contribute to the genetic risk of castration-resistant prostate cancer.

Construct a circRNA/miRNA/mRNA regulatory network to explore potential pathogenesis and therapy options of clear cell renal cell carcinoma

“…In contrast, mir-1205, miR-637, and miR-548p act as tumor suppressor molecules. MiR-1205 can target some downstream gene sits www.nature.com/scientificreports/ to inhibited and promote cell proliferation and invasion in some cancers [43][44][45] . For miR-637, many studies suggest it act as a protective factor to suppress the cancer cells proliferation, invasion and migration by targeting on regulating the expression of AKt1, RING1 or NUPRI in hepatocellular carcinoma, colorectal cancer, glioma, and cervical cancer [45][46][47][48][49] .…”

PVT1 Signaling Is a Mediator of Cancer Progression

“…Consistently, PVT1 is overexpressed in cancer cells compared to normal non-tumorigenic epithelial cells. It is found to be upregulated in bladder (24), breast (25–27), cervical (28), colon (29), colorectal (30, 31), gastric (32–35), lung (36–41), pancreatic (42), and prostate cancer (43–46), as well as clear cell renal cell carcinoma (18), esophageal squamous cell carcinoma (SCC) (20, 47), glioma (48–50), head and neck SCC, hepatocellular carcinoma (51–55), laryngeal SCC (56), malignant pleural mesothelioma (57), osteosarcoma (58–60), and papillary thyroid carcinoma (61), melanoma (62). Further, data from The Cancer Genome Atlas (TCGA) and independent analysis of human clinical tissue samples showed elevated PVT1 expression in cancer tissues in comparison to adjacent normal tissue or matched normal tissue (27, 31, 32, 45, 50).…”

CRISPR/Cas9: A powerful genome editing technique for the treatment of cancer cells with present challenges and future directions

“…The brown box represents the activation of different tumor suppressor genes. The orange box characterizes the inhibition/suppression of drug-resistance genes by CRISPR/Cas9 in solid tumors [ 31 , 35 , 45 , 70 , 74 , [115] , [116] , [117] , [118] , [119] , [120] , [121] , [122] , [123] , [124] , [125] , [126] , [127] , [128] ]. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)…”