Xiaoyong Huang - Academia.edu (original) (raw)

Papers by Xiaoyong Huang

Oncotarget, Jan 4, 2015

MicroRNA contribute to tumor radiation resistance, which is an important clinical problem, and th... more MicroRNA contribute to tumor radiation resistance, which is an important clinical problem, and thus we are interested in identifying and characterizing their function. We demonstrate that miR-620 contributes to radiation resistance in cancer cells by increasing proliferation, and decreasing the G2/M block. We identify the hydroxyprostaglandin dehydrogenase 15-(nicotinamide adenine dinucleotide) (HPGD/15-PGDH) tumor suppressor gene as a direct miR-620 target, which results in increased prostaglandin E2 (PGE2) levels. Furthermore, we show that siRNA targeting of HPGD or administration of exogenous PGE2 recapitulates radioresistance. Targeting of the EP2 receptor that responds to PGE2 using pharmacological or genetic approaches, abrogates radioresistance. Tumor xenograft experiments confirm that miR-620 increases proliferation and tumor radioresistance in vivo. Regulation of PGE2 levels via targeting of HPGD by miR-620 is an innovative manner by which a microRNA can induce radiation re...

World Journal of Gastroenterology, 2014

To investigate the function of Pea3 in colorectal carcinoma (CRC) invasion and metastatic potential.

BMC Cancer, 2014

Background: Most cancer patients are treated with radiotherapy, but the treatment can also damage... more Background: Most cancer patients are treated with radiotherapy, but the treatment can also damage the surrounding normal tissue. Acute skin damage from cancer radiotherapy diminishes patients' quality of life, yet effective biological interventions for this damage are lacking. Protecting microvascular endothelial cells from irradiation-induced perturbations is emerging as a targeted damage-reduction strategy. Since Angiopoetin-1 signaling through the Tie2 receptor on endothelial cells opposes microvascular perturbations in other disease contexts, we used a preclinical Angiopoietin-1 mimic called Vasculotide to investigate its effect on skin radiation toxicity using a preclinical model.

Cancer Science, 2007

That tumors lack innervation is dogma in the field of pathology, but the molecular determinants o... more That tumors lack innervation is dogma in the field of pathology, but the molecular determinants of this phenomenon remain elusive. We studied the effects of conditioned media from Colon 26 and B16 mouse tumor cell lines on the axonal outgrowth and cellular differentiation of embryonic Institute of Cancer Research (ICR) mouse dorsal root ganglion cells. Tumor-conditioned media suppressed dorsal root ganglion axonal extension but had no effect on neuronal or glial differentiation. We found that the tumor cells expressed most of the class 3 semaphorins -axon guidance molecules. Blocking the activity of class 3 semaphorins with the soluble receptor neuropilin-1 significantly counteracted the tumor-induced inhibition of axonal extension. Together, these results suggest a role for tumor-secreted class 3 semaphorins in selectively inhibiting axonal outgrowth of dorsal root ganglion neurons. (Cancer Sci 2007; 98: 1192-1197)

Cancer Research, 2007

EphB4 receptor and its ligand ephrinB2 play an important role in vascular development during embr... more EphB4 receptor and its ligand ephrinB2 play an important role in vascular development during embryogenesis. In blood vessels, ephrinB2 is expressed in arterial endothelial cells (EC) and mesenchymal supporting cells, whereas EphB4 is only expressed in venous ECs. Previously, we reported that OP9 stromal cells, which support the development of both arterial and venous ECs, in which EphB4 was overexpressed, could inhibit ephrinB2-positive (ephrinB2 + ) EC development in an embryonic tissue organ culture system. Although the EphB4 receptor is expressed in a variety of tumor cells, its exact function in regulating tumor progression has not been clearly shown. Here we found that overexpression of EphB4 in B16 melanoma cells suppressed tumor growth in a s.c. transplantation tumor model. Histologic examination of these tumors revealed that EphB4 overexpression in B16 cells selectively suppressed arterial ephrinB2 + EC development. By coculturing ephrinB2-expressing SV40-transformed mouse ECs (SVEC) with EphB4-overexpressing B16 cells, we found that EphB4 induced the apoptosis of SVECs. However, ephrinB2 did not induce the apoptosis of EphB4-overexpressing B16 cells. Based on results from these experiments, we concluded that EphB4 overexpression in B16 tumor cells suppresses the survival of arterial ECs in tumors by a reverse signaling via ephrinB2.

Cancer Research, 2013

Radiation resistance poses a major clinical challenge in cancer treatment, but little is known ab... more Radiation resistance poses a major clinical challenge in cancer treatment, but little is known about how microRNA (miR) may regulate this phenomenon. In this study, we used next-generation sequencing to perform an unbiased comparison of miR expression in PC3 prostate cancer cells rendered resistant to fractionated radiation treatment. One miR candidate found to be upregulated by ionizing radiation was miR-95, the enforced expression of which promoted radiation resistance in a variety of cancer cells. miR-95 overexpression recapitulated an aggressive phenotype including increased cellular proliferation, deregulated G 2 -M checkpoint following ionizing radiation, and increased invasive potential. Using combined in silico prediction and microarray expression analyses, we identified and validated the sphingolipid phosphatase SGPP1, an antagonist of sphingosine-1phosphate signaling, as a target of miR-95 that promotes radiation resistance. Consistent with this finding, cell treatment with FTY720, a clinically approved small molecule inhibitor of S1P signaling, sensitized miR-95 overexpressing cells to radiation treatment. In vivo assays extended the significance of these results, showing that miR-95 overexpression increased tumor growth and resistance to radiation treatment in tumor xenografts. Furthermore, reduced tumor necrosis and increased cellular proliferation were seen after radiation treatment of miR-95 overexpressing tumors compared with control tumors. Finally, miR-95 expression was increased in human prostate and breast cancer specimens compared with normal tissue. Together, our work reveals miR-95 expression as a critical determinant of radiation resistance in cancer cells. Cancer Res; 73(23); 6972-86. Ó2013 AACR.

PLoS ONE, 2014

The noncluster homeobox gene HOX11/TLX1 (TLX1) is detected at the breakpoint of the t(10;14)(q24;... more The noncluster homeobox gene HOX11/TLX1 (TLX1) is detected at the breakpoint of the t(10;14)(q24;q11) chromosome translocation in patients with T cell acute lymphoblastic leukemia (T-ALL). This translocation results in the inappropriate expression of TLX1 in T cells. The oncogenic potential of TLX1 was demonstrated in IgHm-TLX1 Tg mice which develop mature B cell lymphoma after a long latency period, suggesting the requirement of additional mutations to initiate malignancy. To determine whether dysregulation of genes involved in the DNA damage response contributed to tumor progression, we crossed IgHm-TLX1 Tg mice with mice deficient in the DNA repair enzyme DNA-PK (Prkdc Scid/Scid mice). IgHm-TLX1 Tg Prkdc Scid/Scid mice developed T-ALL and acute myeloid leukemia (AML) with reduced latency relative to control Prkdc Scid/Scid mice. Further analysis of thymi from premalignant mice revealed greater thymic cellularity concomitant with increased thymocyte proliferation and decreased apoptotic index. Moreover, premalignant and malignant thymocytes exhibited impaired spindle checkpoint function, in association with aneuploid karyotypes. Gene expression profiling of premalignant IgHm-TLX1 Tg Prkdc Scid/Scid thymocytes revealed dysregulated expression of cell cycle, apoptotic and mitotic spindle checkpoint genes in double negative 2 (DN2) and DN3 stage thymocytes. Collectively, these findings reveal a novel synergy between TLX1 and impaired DNA repair pathway in leukemogenesis.