Publications by authors named "Ren-Yu Hu"

10 Publications

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Biomarker discovery in highly invasive lung cancer cell through proteomics approaches.

Cell Biochem Funct 2021 Apr 1;39(3):367-379. Epub 2020 Nov 1.

Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan.

Lung cancer is one of the leading causes of cancer-related death worldwide. The most common type of lung cancer is non-small cell lung cancer (NSCLC). When NSCLC is detected, patients are typically already in a metastatic stage. Metastasized cancer is a major obstacle of effective treatment and understanding the mechanisms underlying metastasis is critical to treat cancer. Herein, we selected an invasive subpopulation from the human lung cancer cell line A549 using the transwell system and named it as A549-I5. Invasive and migratory activities of this cell line were analysed using wound healing, invasion, and migration assays. In addition, epithelial-mesenchymal transition (EMT) markers, such as Snail 1, Twist, Vimentin, N-cadherin and E-cadherin, were assessed through immunoblotting. In comparison to A549 cells, the invasive A549-I5 lung cancer cells had enhanced invasiveness, motility and EMT marker expression. Proteomic analysis identified 83 significantly differentially expressed proteins in A549-I5 cells. These identified proteins were classified according to their cellular functions and most were involved in cytoskeleton, redox regulation, protein degradation and protein folding. In summary, our results provide potential diagnostic markers and therapeutic candidates for the treatment of NSCLC metastasis. SIGNIFICANCE OF THE STUDY: When NSCLC is detected, most patients are already in a metastatic stage. Herein, we selected an invasive subpopulation from a human lung cancer cell line which had increased EMT markers as well as high wound healing, invasion and migration abilities. Proteomic analysis identified numerous proteins associated with functions in cytoskeleton, redox regulation, protein degradation and protein folding that were differentially expressed in these cells. These results may provide potential diagnostic markers and therapeutic candidates for the treatment of NSCLC metastasis.
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http://dx.doi.org/10.1002/cbf.3599DOI Listing
April 2021

Proteomic Analysis of Metastasis-Specific Biomarkers in Pancreatic Cancer: Galectin-1 Plays an Important Metastatic Role in Pancreatic Cancer.

J Pharm Biomed Anal 2020 Jul 25;186:113300. Epub 2020 Apr 25.

Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan. Electronic address:

Cancer metastasis is the major cause of death in pancreatic cancer. We have established a pair of pancreatic ductal adenocarcinoma cell line, PANC1 and invasive PANC1-I5, as a model system toinvestigate the metastatic mechanism as well as potential therapeutic targets in pancreatic cancer. We used proteomic analysis based on two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to examine the global protein expression alterations between PANC1 and PANC1-I5. Proteomic study revealed that 88 proteins are differentially expressed between PANC1-I5 and PANC1 cells, and further functional evaluations through protein expression validation, gene knockout, migration and invasion analysis revealed that galectin-1 is one of the potential players in modulating pancreatic cancer metastasis. To conclude, we have identified numerous proteins might be associated with pancreatic cancer invasiveness in the pancreatic cancer model.
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http://dx.doi.org/10.1016/j.jpba.2020.113300DOI Listing
July 2020

Speckle-suppressed full-field imaging through a scattering medium using a supercontinuum.

Opt Express 2016 Nov;24(23):26338-26343

We demonstrate speckle-suppressed full-field imaging through a scattering medium using incoherent supercontinuum (SC) illumination. The patterns in images obtained using SC illumination were found to be more easily identifiable than those in images acquired using coherent direct laser illumination due to the speckle suppression. Even when the optical depth reached 12.3, the patterns remained identifiable. As one of the potential applications, we also demonstrated the imaging for a high-pressure diesel spray using SC illumination.
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http://dx.doi.org/10.1364/OE.24.026338DOI Listing
November 2016

MMP-13 is involved in oral cancer cell metastasis.

Oncotarget 2016 03;7(13):17144-61

Department of Medical Sciences and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan.

The oral cancer cell line OC3-I5 with a highly invasive ability was selected and derived from an established OSCC line OC3. In this study, we demonstrated that matrix metalloproteinases protein MMP-13 was up-regulated in OC3-I5 than in OC3 cells. We also observed that expression of epithelial-mesenchymal transition (EMT) markers including Twist, p-Src, Snail1, SIP1, JAM-A, and vinculin were increased in OC3-I5 compared to OC3 cells, whereas E-cadherin expression was decreased in the OC3-I5 cells. Using siMMP-13 knockdown techniques, we showed that siMMP-13 not only reduced the invasion and migration, but also the adhesion abilities of oral cancer cells. In support of the role of MMP-13 in metastasis, we used MMP-13 expressing plasmid-transfected 293T cells to enhance MMP-13 expression in the OC3 cells, transplanting the MMP-13 over expressing OC3 cells into nude mice led to enhanced lung metastasis. In summary, our findings show that MMP-13 promotes invasion and metastasis in oral cancer cells, suggesting altered expression of MMP-13 may be utilized to impede the process of metastasis.
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http://dx.doi.org/10.18632/oncotarget.7942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941377PMC
March 2016

Erratum to: PGRMC1 contributes to doxorubicin-induced chemoresistance in MES-SA uterine sarcoma.

Cell Mol Life Sci 2015 Jun;72(12):2411-3

Institute of Bioinformatics and Structural Biology, National Tsing Hua University, No. 101, Kuang-Fu Rd. Sec. 2, Hsin-chu, 30013, Taiwan.

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http://dx.doi.org/10.1007/s00018-015-1852-zDOI Listing
June 2015

PGRMC1 contributes to doxorubicin-induced chemoresistance in MES-SA uterine sarcoma.

Cell Mol Life Sci 2015 Jun 18;72(12):2395-409. Epub 2015 Jan 18.

Institute of Bioinformatics and Structural Biology, National Tsing Hua University, No. 101, Kuang-Fu Rd. Sec. 2, Hsin-chu, 30013, Taiwan.

Chemotherapy is one of the major categories of medical oncology and a primary tumor treatment; however, the effectiveness of chemotherapy is restricted by drug resistance. Overcoming resistance to chemotherapy and investigating molecular targeted therapies are challenges currently faced during resistance management. Progesterone receptor membrane component 1 (PGRMC1) is an adapter protein mediating cholesterol synthesis, steroid signaling, and cytochrome p450 activation. Attention has recently focused on the role of PGRMC1 in cell survival, anti-apoptosis, and damage response. In the present study, we used knockdown and overexpression approaches in the following set of uterine sarcoma models to further evaluate the role of PGRMC1 in drug resistance: the doxorubicin-sensitive MES-SA cells and the doxorubicin-resistant MES-SA/DxR-2 µM and MES-SA/DxR-8 µM cells (with different levels of doxorubicin resistance). PGRMC1 repressed doxorubicin-induced cytotoxicity and exhibited an anti-apoptotic effect; it also promoted cell proliferation and cell cycle progression to the S phase. Of note, PGRMC1 overexpression led to the epithelial-mesenchymal transition (EMT) of the sensitive MES-SA cells, thus facilitating their migration and invasion. The combination of PGRMC1 knockdown and the P-glycoprotein inhibitor verapamil significantly decreased the viability of P-glycoprotein-overexpressing MES-SA/DxR-8 μM cells after doxorubicin treatment. Taken together, our results show that PGRMC1 contributed to chemoresistance through cell proliferation, anti-apoptosis, and EMT induction, leading to the suggestion that PGRMC1 may serve as a therapeutic target in combination with an inhibitor in different drug resistance pathways and indicating the usefulness of predictive resistance biomarkers in uterine sarcoma.
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http://dx.doi.org/10.1007/s00018-014-1831-9DOI Listing
June 2015

Identification of up- and down-regulated proteins in doxorubicin-resistant uterine cancer cells: reticulocalbin-1 plays a key role in the development of doxorubicin-associated resistance.

Pharmacol Res 2014 Dec 19;90:1-17. Epub 2014 Sep 19.

Institute of Bioinformatics and Structural Biology and Department of Medical Sciences, National Tsing Hua University, Hsinchu, Taiwan. Electronic address:

Drug resistance is a frequent cause of failure in cancer chemotherapy treatments. In this study, a pair of uterine sarcoma cancer lines, MES-SA, and doxorubicin-resistant partners, MES-SA/DxR-2μM cells and MES-SA/DxR-8μM cells, as a model system to investigate resistance-dependent proteome alterations and to identify potential therapeutic targets. We used two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to perform this research and the results revealed that doxorubicin-resistance altered the expression of 208 proteins in which 129 identified proteins showed dose-dependent manners in response to the levels of resistance. Further studies have used RNA interference, H2A.X phosphorylation assay, cell viability analysis, and analysis of apoptosis against reticulocalbin-1 (RCN1) proteins, to prove its potency on the formation of doxorubicin resistance as well as the attenuation of doxorubicin-associated DNA double strand breakage. To sum up, our results provide useful diagnostic markers and therapeutic candidates such as RCN1 for the treatment of doxorubicin-resistant uterine cancer.
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http://dx.doi.org/10.1016/j.phrs.2014.08.007DOI Listing
December 2014

Biomarker discovery for neuroendocrine cervical cancer.

Electrophoresis 2014 Jul 5;35(14):2039-45. Epub 2014 Jun 5.

Department of Medical Sciences, Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan.

Neuroendocrine cervical cancer is an aggressive but rare form of cervical cancer. The majority of neuroendocrine cervical cancer patients present with advanced-stage diseases. However, the limited numbers of neuroendocrine tumor markers are insufficient for clinical purposes. Thus, we used a proteomic approach combining lysine labeling 2D-DIGE and MALDI-TOF MS to investigate the biomarkers for neuroendocrine cervical cancer. By analyzing the global proteome alteration between the neuroendocrine cervical cancer line (HM-1) and non-neuroendocrine cervical cancer lines (CaSki cells, ME-180 cells, and Hela cells), we identified 82 proteins exhibiting marked changes between HM-1 and CaSki cells, and between ME-180 and Hela cells. Several proteins involved in protein folding, cytoskeleton, transcription control, signal transduction, glycolysis, and redox regulation exhibited significant changes in abundance. Proteomic and immunoblot analyses indicated respective 49.88-fold and 25-fold increased levels of transgelin in HM-1 cells compared with that in other non-neuroendocrine cervical cancer cell lines, implying that transgelin is a biomarker for neuroendocrine cervical cancer. In summary, we used a comprehensive neuroendocrine/non-neuroendocrine cervical cancer model based proteomic approach for identifying neuroendocrine cervical cancer markers, which might contribute to the prognosis and diagnosis of neuroendocrine cervical cancer.
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http://dx.doi.org/10.1002/elps.201400014DOI Listing
July 2014

Quercetin-induced cardioprotection against doxorubicin cytotoxicity.

J Biomed Sci 2013 Dec 20;20:95. Epub 2013 Dec 20.

Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan.

Background: Cancer has continually been the leading cause of death worldwide for decades. Thus, scientists have actively devoted themselves to studying cancer therapeutics. Doxorubicin is an efficient drug used in cancer therapy, but also produces reactive oxygen species (ROS) that induce severe cytotoxicity against heart cells. Quercetin, a plant-derived flavonoid, has been proven to contain potent antioxidant and anti-inflammatory properties. Thus, this in vitro study investigated whether quercetin can decrease doxorubicin-induced cytotoxicity and promote cell repair systems in cardiomyocyte H9C2 cells.

Results: Proteomic analysis and a cell biology assay were performed to investigate the quercetin-induced responses. Our data demonstrated that quercetin treatment protects the cardiomyocytes in a doxorubicin-induced heart damage model. Quercetin significantly facilitated cell survival by inhibiting cell apoptosis and maintaining cell morphology by rearranging the cytoskeleton. Additionally, 2D-DIGE combined with MALDI-TOF MS analysis indicated that quercetin might stimulate cardiomyocytes to repair damage after treating doxorubicin by modulating metabolic activation, protein folding and cytoskeleton rearrangement.

Conclusion: Based on a review of the literature, this study is the first to report detailed protective mechanisms for the action of quercetin against doxorubicin-induced cardiomyocyte toxicity based on in-depth cell biology and proteomic analysis.
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http://dx.doi.org/10.1186/1423-0127-20-95DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898810PMC
December 2013