Intergenic Splicing between Four Adjacent Genes () Gives Rise to Variant UGT Proteins That Inhibit Glucuronidation via Protein-Protein Interactions.

Recent studies have investigated alternative splicing profiles of UDP-glucuronosyltransferase genes and identified over 130 different alternatively spliced UGT transcripts. Although genes are highly clustered, the formation of chimeric transcripts by intergenic splicing between two or more genes has not yet been reported. This study identified 12 chimeric transcripts (chimeras A-L) containing exons from two or three genes of the four neighboring genes (, , , and ) in human liver and prostate cancer cells.

Regulation of UDP-Glucuronosyltransferase 2B15 by miR-331-5p in Prostate Cancer Cells Involves Canonical and Noncanonical Target Sites.

is an important androgen-metabolizing UDP-glucuronosyltransferase (UGT) and the mechanisms controlling its expression are of considerable interest. Recent studies showed that miR-376c regulates in prostate cancer cells via a canonical target site in the 3' untranslated region (). The also contains a canonical miR-331-5p target site; previous work indicated that deleting this site reduced, but did not abolish, the ability of miR-331-5p to repress a luciferase reporter carrying the We report here the discovery and characterization of a second, noncanonical miR-331-5p target site in the miR-331-5p-mediated repression of a reporter was partly inhibited by mutating either of the two miR-331-5p target sites separately, but completely abolished by mutating the two sites simultaneously, indicating that the two sites act cooperatively.

Regulation of UDP-Glucuronosyltransferases UGT2B4 and UGT2B7 by MicroRNAs in Liver Cancer Cells.

The transcriptional regulation of UDP-glucuronosyltransferases and has been well studied using liver cancer cell lines, and post-transcriptional regulation of these two by microRNA (miRNA/miR) miR-216b-5p was recently reported. This study describes novel miRNA-mediated regulation of UGT2B4 and UGT2B7 in liver cancer cells. Bioinformatic analyses identified a putative miR-3664-3p binding site in the UGT2B7 3'-untranslated region (UTR) and binding sites for both miR-135a-5p and miR-410-3p in the UGT2B4 3'-UTR.

Regulation of Human UGT2B15 and UGT2B17 by miR-376c in Prostate Cancer Cell Lines.

Given the prime importance of UDP-glucuronosyltransferase (UGT) 2B15 and UGT2B17 in inactivating testosterone and dihydrotestosterone, control of their expression and activity in the prostate is essential for androgen signaling homeostasis in this organ. Although several studies provide evidence of transcriptional control of UGT2B15 and UGT2B17 by various endogenous and exogenous compounds, potential post-transcriptional regulation of UGT2B15 and UGT2B17 by microRNAs (miRs) in prostate cancer cells has not been examined. The present study identified a putative miR-376c target site in the 3'-untranslated regions (UTRs) of both UGT2B15 and UGT2B17 mRNAs.

Identification of androgen receptor splice variant transcripts in breast cancer cell lines and human tissues.

The androgen receptor (AR) is widely expressed in human tissues and has biological function in many male and female organs. In particular, the AR plays a critical role in the biology and pathology of the prostate gland. AR activity inhibits breast growth and has pleiotropic actions in breast cancer that are subtype-dependent.

The orphan nuclear receptor LRH-1 and ERα activate GREB1 expression to induce breast cancer cell proliferation.

Background: Liver Receptor Homolog 1 (LRH-1, NR5A2) is an orphan nuclear receptor that is over-expressed in cancers in tissues such as the breast, colon and pancreas. LRH-1 plays important roles in embryonic development, steroidogenesis and cholesterol homeostasis. In tumor cells, LRH-1 induces proliferation and cell cycle progression.