Entity

Time filter

Source Type

Fort Worth, TX, United States

Rajendiran S.,University of North Texas Health Science Center | Parwani A.V.,UPMC Shadyside Hospital | Hare R.J.,Plaza Medical Center | Dasgupta S.,University of North Texas Health Science Center | And 4 more authors.
Molecular Cancer | Year: 2014

Background: MicroRNAs (miRNAs) are crucial molecules that regulate gene expression and hence pathways that are key to prostate cancer progression. These non-coding RNAs are highly deregulated in prostate cancer thus facilitating progression of the disease. Among the many genes that have gained importance in this disease, Migration and invasion enhancer 1 (MIEN1), a novel gene located next to HER2/neu in the 17q12 amplicon of the human chromosome, has been shown to enhance prostate cancer cell migration and invasion, two key processes in cancer progression. MIEN1 is differentially expressed between normal and cancer cells and tissues. Understanding the regulation of MIEN1 by microRNA may enable development of better targeting strategies. Methods: The miRNAs that could target MIEN1 were predicted by in silico algorithms and microarray analysis. The validation for miRNA expression was performed by qPCR and northern blotting in cells and by in situ hybridization in tissues. MIEN1 and levels of other molecules upon miRNA regulation was determined by Western blotting, qPCR, and immunofluorescence. The functional effects of miRNA on cells were determined by wound healing cell migration, Boyden chamber cell invasion, clonal and colony formation assays. For knockdown or overexpression of the miRNA or overexpression of MIEN1 3'UTR, cells were transfected with the oligomiRs and plasmids, respectively. Results: A novel miRNA, hsa-miR-940 (miR-940), identified and validated to be highly expressed in immortalized normal cells compared to cancer cells, is a regulator of MIEN1. Analysis of human prostate tumors and their matched normal tissues confirmed that miR-940 is highly expressed in the normal tissues compared to its low to negligible expression in the tumors. While MIEN1 is a direct target of miR-1, miR-940 alters MIEN1 RNA, in a quantity as well as cell dependent context, along with altering its downstream effectors. The miR-940 inhibited migratory and invasive potential of cells, attenuated their anchorage-independent growth ability, and increased E-cadherin expression, implicating its role in mesenchymal-to-epithelial transition (MET). Conclusions: These results, for the first time, implicate miR-940, a regulator of MIEN1, as a promising novel diagnostic and prognostic tool for prostate cancer. © Rajendiran et al.; licensee BioMed Central Ltd. Source


Rajendiran S.,University of North Texas Health Science Center | Parwani A.V.,UPMC Shadyside Hospital | Hare R.J.,Plaza Medical Center | Dasgupta S.,University of North Texas Health Science Center | And 2 more authors.
Molecular Cancer | Year: 2015

Background: MicroRNAs (miRNAs) are crucial molecules that regulate gene expression and hence pathways that are key to prostate cancer progression. These non-coding RNAs are highly deregulated in prostate cancer thus facilitating progression of the disease. Among the many genes that have gained importance in this disease, Migration and invasion enhancer 1 (MIEN1), a novel gene located next to HER2/neu in the 17q12 amplicon of the human chromosome, has been shown to enhance prostate cancer cell migration and invasion, two key processes in cancer progression. MIEN1 is differentially expressed between normal and cancer cells and tissues. Understanding the regulation of MIEN1 by microRNA may enable development of better targeting strategies. Methods: The miRNAs that could target MIEN1 were predicted by in silico algorithms and microarray analysis. The validation for miRNA expression was performed by qPCR and northern blotting in cells and by in situ hybridization in tissues. MIEN1 and levels of other molecules upon miRNA regulation was determined by Western blotting, qPCR, and immunofluorescence. The functional effects of miRNA on cells were determined by wound healing cell migration, Boyden chamber cell invasion, clonal and colony formation assays. For knockdown or overexpression of the miRNA or overexpression of MIEN1 3'UTR, cells were transfected with the oligomiRs and plasmids, respectively. Results: A novel miRNA, hsa-miR-940 (miR-940), identified and validated to be highly expressed in immortalized normal cells compared to cancer cells, is a regulator of MIEN1. Analysis of human prostate tumors and their matched normal tissues confirmed that miR-940 is highly expressed in the normal tissues compared to its low to negligible expression in the tumors. While MIEN1 is a direct target of miR-940, miR-940 alters MIEN1 RNA, in a quantity as well as cell dependent context, along with altering its downstream effectors. The miR-940 inhibited migratory and invasive potential of cells, attenuated their anchorage-independent growth ability, and increased E-cadherin expression, implicating its role in mesenchymal-to-epithelial transition (MET). Conclusions: These results, for the first time, implicate miR-940, a regulator of MIEN1, as a promising novel diagnostic and prognostic tool for prostate cancer. © 2014 Rajendiran et al.; licensee BioMed Central Ltd. Source


Rajendiran S.,University of North Texas Health Science Center | Kpetemey M.,University of North Texas Health Science Center | Maji S.,University of North Texas Health Science Center | Gibbs L.D.,University of North Texas Health Science Center | And 5 more authors.
Cancer Biology and Therapy | Year: 2015

Oral squamous cell carcinoma is a highly malignant tumor with the potential to invade local and distant sites and promote lymph node metastasis. Major players underlying the molecular mechanisms behind tumor progression are yet to be fully explored. Migration and invasion enhancer 1 (MIEN1), a novel protein overexpressed in various cancers, facilitates cell migration and invasion. In the present study we investigated the expression and role of MIEN1 in oral cancer progression using an in vitro model, patient derived oral tissues and existing TCGA data. Expression analysis using immortalized normal and cancer cells demonstrated increased expression of MIEN1 in cancer. Assays performed after MIEN1 knockdown in OSC-2 cells showed decreased migration, invasion and filopodia formation; while MIEN1 overexpression in DOK cells increased these characteristics and also up-regulated some Akt/NF-κB effectors, thereby suggesting an important role for MIEN1 in oral cancer progression. Immunohistochemical staining and analyses of oral tissue specimens, collected from patients over multiple visits, revealed significantly more staining in severe dysplasia and squamous cell carcinoma compared to mildly dysplastic or hyperplastic tissues. Finally, this was corroborated with the TCGA dataset, where MIEN1 expression was not only higher in intermediate and high grade cancer with significantly lower survival but also correlated with smoking. In summary, we demonstrate that MIEN1 expression not only positively correlates with oral cancer progression but also seems to be a critical molecular determinant in migration and invasion of oral cancer cells, thereby, playing a possible role in their metastatic dissemination. © 2015 Taylor & Francis Group, LLC. Source


Yurvati A.H.O.,University of North Texas Health Science Center | Thompson J.B.,University of North Texas Health Science Center | Woods T.N.,University of North Texas Health Science Center | Woods T.N.,Plaza Medical Center
Journal of the American Osteopathic Association | Year: 2013

Splenosis is a rare occurrence that is defined as autotransplantation of splenic tissue usually after splenic rupture due to trauma and subsequent splenectomy. Although splenosis most commonly occurs in the abdomen, the authors report a rare case of thoracic splenosis after remote thoracoabdominal trauma. A 62-year-old woman was found to have lower-lobe, pleural-based nodular lesions in juxtaposition to the posteromedial segment of the lung during workup for an abdominal hernia. Surgical excision of the mass confirmed the diagnosis of ectopic splenic tissue, and splenosis was diagnosed. This woman was among the rare 18% of people who are found to have splenosis in the intrathoracic space. In the workup of pulmonary nodules in patients with a history of trauma, splenosis should be a consideration. © 2013 American Osteopathic Association. Source

Discover hidden collaborations