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Pou6f2 is a genetic connection between central corneal thickness (CCT) in the mouse and a risk factor for developing primary open-angle glaucoma. POU6F2 is also a risk factor for several conditions in humans, including glaucoma, myopia, and dyslexia. Recent findings demonstrate that POU6F2-positive retinal ganglion cells (RGCs) comprise a number of RGC subtypes in the mouse, some of which also co-stain for Cdh6 and Hoxd10. These POU6F2-positive RGCs appear to be novel of ON–OFF directionally selective ganglion cells (ooDSGCs) that do not co-stain with CART or SATB2 (typical ooDSGCs markers). These POU6F2-positive cells are sensitive to damage caused by elevated intraocular pressure. In the DBA/2J mouse glaucoma model, heavily-labeled POU6F2 RGCs decrease by 73% at 8 months of age compared to only 22% loss of total RGCs (labeled with RBPMS). Additionally, Pou6f2 −/− mice suffer a significant loss of acuity and spatial contrast sensitivity along with an 11.4% loss of total RGCs. In the rhesus macaque retina, POU6F2 labels the large parasol ganglion cells that form the magnocellular (M) pathway. The association of POU6F2 with the M-pathway may reveal in part its role in human glaucoma, myopia, and dyslexia.

The aim of this study was to explore the molecular mechanism of lncRNA POU6F2‐AS2 in proliferation and drug resistance of colon cancer. Total paired 70 colon cancer and adjacent normal tissues were collected from colon cancer patients. Colon cancer and normal colonic epithelial cells were purchased. POU6F2‐AS2 was up‐ or down‐expressed by vectors. LC50 of all cell lines before and after transfection with these plasmids was detected. qRT‐PCR was used to detect the expression of POU6F2‐AS2, miR‐377 and BRD4 before or after transfection. In situ hybridization was also undertaken to detect the level of POU6F2‐AS2. Different concentrations of 5‐Fu (0, 1, 2.5, 5, 10, 20, 40 and 80 μg/mL) were used for 5‐FU insensitivity assay. CCK‐8 and crystal violet staining assay were used for detecting cell proliferation, and flow cytometry was used for identifying cell cycle distribution and apoptosis. In order to detect the fragmented DNA in apoptotic cells, TUNEL assay was used. RNA pull‐down assay and luciferase reporter assay were used to verify the binding site. Rescue assay confirmed the subtractive effect of miR‐377 inhibitors. POU6F2‐AS2 was highly expressed in colon cancer, which was associated with clinical pathology. Up‐regulated POU6F2‐AS2 promoted cell proliferation and cell cycle of colon cancer cells. Overexpression of POU6F2‐AS2 inhibited the expression of miR‐377 and then up‐regulated the expression of BRD4. Up‐regulated BRD4 ultimately promoted cell proliferation and cell survival Down‐regulated POU6F2‐AS2 showed enhanced sensitivity of 5‐FU. POU6F2‐AS2 promoted cell proliferation and drug resistance in colon cancer by regulating miR‐377/BRD4 gene.

Background Pituitary adenomas (PAs) are one of the most common intracranial tumors; approximately half of PAs are prolactin (PRL)‐secreting PAs (prolactinomas). The genetic alterations prevalent in prolactinomas are unknown. Methods Here, we present a patient with an extremely aggressive and giant prolactinoma accompanied by serious destruction of the surrounding bone mass. This patient exhibited resistance to dopaminergic drugs. Through whole‐genome sequencing, we identified two novel somatic mutations in the POU6F2 gene (NM_001166018.2: c. 839 C>T; NM_001166018.2: c. 875A>G). Results This report is the first to identify these somatic mutations in the POU6F2 gene in a prolactinoma. We found that these two mutations obviously decreased the expression level of POU6F2. Inhibition of POU6F2 activity increased the cell proliferation and PRL secretion in rat pituitary cells, but proliferation and PRL secretion were decreased in cells with POU6F2 overexpression. Conclusions POU6F2 might play a crucial role in the development of prolactinomas and may be a promising target for developing new therapies against prolactinomas. It is the first report of somatic mutation in POU6F2 gene in a prolactinoma. We found that these two mutations obviously decreased the expression level of POU6F2. Inhibition of POU6F2 activity increased the cell proliferation and prolactin (PRL) secretion in rat pituitary cells, the cell proliferation and secretion of PRL were decreased when POU6F2 overexpression was achieved.

Wilms tumor (WT) is a kidney malignancy of childhood characterized by highly heterogeneous genetic alterations. We previously reported the molecular and cytogenetic characterization of a WT (Case 30) carrying an interstitial deletion in chromosome 7p14 between markers D7S555 and D7S668. Loss of heterozygosity (LOH) analyses had revealed that this same region was lost in 8 out of 38 examined WTs, suggesting that the identified interval contains a putative tumor suppressor gene. To confirm this hypothesis, in this work, we analyzed an additional 35 WTs, four of which showed LOH in the region of interest. Furthermore, we were able to more accurately define the extension of the deletion in Case 30, mapping it within an interval not exceeding 390 kb, proximally to D7S555. To date, only a single expressed gene, POU6F2 (the POU domain, class 6, transcription factor 2; also known as RPF1), has been recognized in this interval. Sequencing of the gene in the 12 WTs showing LOH and in a corresponding numbers of WT cases without LOH, led to the identification of two germline nucleotide substitutions. The first occurred in the 5′‐untranslated region, while the second caused an amino acid change in a glutamine repeat domain. These mutations, whose occurrence was not observed in more than 100 control subjects, were detected in two patients showing the loss of the constitutionally wild‐type allele in tumor DNA. Together with the finding of the expression of the POU6F2 mouse homolog in both fetal and adult kidney, our observations suggest that the gene is a tumor suppressor and is involved in hereditary predisposition to WT. Hum Mutat 24:400–407, 2004. © 2004 Wiley‐Liss, Inc.