Combination of ONC201 and TLY012 induces selective, synergistic apoptosis in vitro and significantly delays PDAC xenograft growth in vivo

ABSTRACT It has been found that the circular RNA (circRNA) CDR1as is upregulated in cholangiocarcinoma (CCA) tissues. In this study, we tried to explore the roles of CDR1as in CCA. CDR1as was overexpressed or knocked down in human CCA cells to assess the effects of CDR1as on cell behaviors and tumor xenograft growth. In vitro, the CDR1as level was significantly increased in CCA cell lines. The results showed that CDR1as promoted the cell proliferation, migration, invasion, and activation of the AKT3/mTOR pathway in CCA cells. Moreover, miR-641, a predicted target microRNA (miRNA) of CDR1as, could partially reverse the effects of CDR1as on cell behaviors in CCA cells. Furthermore, CDR1as improved tumor xenograft growth, and it could be attenuated by miR-641 in vivo. Additionally, CDR1as expression was inversely correlated with miR-641 in CCA cells, and miR-641 could directly bind with CDR1as and its target genes, the AKT3 and mTOR genes. Mechanistically, CDR1as could bind with miR-641 and accelerate miR-641 degradation, which possibly leads to the upregulation of the relative mRNA levels of AKT3 and mTOR in RBE cells. In conclusion, our findings indicated that CDR1as might exert oncogenic properties, at least partially, by regulating miR-641 in CCA. CDR1as and miR-641 could be considered therapeutic targets for CCA.

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Effects of MALAT1 on proliferation and apo- ptosis of human non-small cell lung cancer A549 cells in vitro and tumor xenograft growth in vivo by modulating autophagy

Cancer Biomarkers ◽

10.3233/cbm-170917 ◽

2018 ◽

Vol 22 (1) ◽

pp. 63-72 ◽

Cited By ~ 15

Author(s):

Jun Ma ◽

Kaiming Wu ◽

Kuanzhi Liu ◽

Rong Miao

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

A549 Cells ◽

Small Cell ◽

Tumor Xenograft ◽

Small Cell Lung ◽

Xenograft Growth ◽

Tumor Xenograft Growth

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Single-Agent Inhibition of Chk1 Is Antiproliferative in Human Cancer Cell Lines In Vitro and Inhibits Tumor Xenograft Growth In Vivo

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504011x13079697132961 ◽

2011 ◽

Vol 19 (7) ◽

pp. 349-363 ◽

Cited By ~ 19

Author(s):

Kurtis D. Davies ◽

Michael J. Humphries ◽

Francis X. Sullivan ◽

Ira von Carlowitz ◽

Yvan Le Huerou ◽

...

Keyword(s):

Cell Lines ◽

Human Cancer ◽

Single Agent ◽

Tumor Xenograft ◽

Human Cancer Cell ◽

Human Cancer Cell Lines ◽

Xenograft Growth ◽

Tumor Xenograft Growth

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Expression of adrenomedullin in human colorectal tumors and its role in cell growth and invasion in vitro and in xenograft growth in vivo

Cancer Medicine ◽

10.1002/cam4.51 ◽

2013 ◽

Vol 2 (2) ◽

pp. 196-207 ◽

Cited By ~ 17

Author(s):

Emilie Nouguerède ◽

Caroline Berenguer ◽

Stéphane Garcia ◽

Bahia Bennani ◽

Christine Delfino ◽

...

Keyword(s):

Cell Growth ◽

Colorectal Tumors ◽

Xenograft Growth

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Neutralization of Adrenomedullin Inhibits the Growth of Human Glioblastoma Cell Lines in Vitro and Suppresses Tumor Xenograft Growth in Vivo

American Journal Of Pathology ◽

10.1016/s0002-9440(10)62555-2 ◽

2002 ◽

Vol 160 (4) ◽

pp. 1279-1292 ◽

Cited By ~ 89

Author(s):

L'Houcine Ouafik ◽

Samantha Sauze ◽

Françoise Boudouresque ◽

Olivier Chinot ◽

Christine Delfino ◽

...

Keyword(s):

Cell Lines ◽

Tumor Xenograft ◽

Glioblastoma Cell ◽

Human Glioblastoma ◽

Human Glioblastoma Cell ◽

Xenograft Growth ◽

Tumor Xenograft Growth ◽

Glioblastoma Cell Lines

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LncRNA RHPN1-AS1 promotes cholangiocarcinoma progression and predicts poor clinical outcome through miR-345-5p/YAP1 axis

10.21203/rs.3.rs-58822/v1 ◽

2020 ◽

Author(s):

Lifeng Ma ◽

Tao Li ◽

Guochao Liu ◽

Jianlong Wang ◽

Zhaoqiang Yin ◽

...

Keyword(s):

Cell Proliferation ◽

Clinical Practice ◽

Clinical Outcome ◽

Carcinoma Cell ◽

Poor Clinical Outcome ◽

Xenograft Growth ◽

Poor Outcome ◽

New Strategies

Abstract Background LncRNAs have proven to be involved in the initiation and progression of cholangiocarcinoma (CCA), although the mechanism by which this occurs remains unknown. Methods The current study reveals that RHPN1-AS1 was overexpressed in CCA patient samples, which predicted poor outcome of CCA patients. RHPN1-AS1 increased in vitro pancreatic carcinoma cell proliferation as well as promoted xenograft growth in vivo. Mechanistically, DANCR upregulated expression of YAP1 by competitively binding to miR-345-5p. Importantly, RHPN1-AS1 level was positively correlated with YAP1 expression level in CCA tissues. Moreover, YAP1 overexpression could predicted a poor outcome of CCA patients. Results Taken together, our results suggested that RHPN1-AS1 might be a remarkable biomarker to evaluate prognosis in CCA. Conclusion The RHPN1-AS1/YAP1 axis may provide new strategies for CCA clinical practice.

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TCF21 inhibits tumor-associated angiogenesis and suppresses the growth of cholangiocarcinoma by targeting PI3K/Akt and ERK signaling

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00264.2018 ◽

2019 ◽

Vol 316 (6) ◽

pp. G763-G773 ◽

Cited By ~ 2

Author(s):

Hua-Xin Duan ◽

Bo-Wen Li ◽

Xin Zhuang ◽

Lu-Ting Wang ◽

Qian Cao ◽

...

Keyword(s):

Endothelial Cells ◽

Transcription Factor ◽

Protein Kinase ◽

Cell Lines ◽

Protein Kinase B ◽

Tube Formation ◽

Phosphatidylinositol 3 Kinase ◽

Xenograft Growth

Tumor-associated angiogenesis plays a critical role in the pathogenesis of cholangiocarcinoma (CCA). In this study, we examined the biological effects and molecular mechanisms of transcription factor 21 (TCF21) on CCA-associated angiogenesis. TCF21 expression was compared between 15 pairs of peritumor normal tissues and CCA tissues and also between normal bile duct epithelial cells and two CCA cell lines (QBC-939 and TFK-1) using real-time PCR and Western blot. With the use of both CCA cell lines as the model system, we stably expressed TCF21 by lentiviral transduction (Lv-TCF21). In vivo, we monitored xenograft growth from different CCA cells, measured tumor-associated angiogenesis by histological analysis, and determined the expressions and circulatory levels of VEGFA and PDGF-BB by immunohistochemistry and ELISA, respectively. In vitro, we assessed the effects of conditioned medium collected from different CCA cells on the viability, migration, and tube formation of endothelial cells and explored the significance of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), as well as ERK1/2 signaling in this process. TCF21 was significantly downregulated in CCA tissues or cell lines. Ectopic expression of TCF21 in CCA cells inhibited xenograft growth or tumor-associated angiogenesis in vivo and targeted the expression and secretion of proangiogenic factors, VEGFA and PDGF-BB. In vitro, the conditioned medium collected from Lv-TCF21 CCA cells significantly reduced the viability, migration, and tube formation of endothelial cells. On the molecular level, the targeting of PI3K/Akt and ERK1/2 signaling mediated the anti-angiogenic activity of TCF21. TCF21 presents growth-inhibitory and anti-angiogenic activities, and thus the elevation of TCF21 expression may provide therapeutic benefits for CCA. NEW & NOTEWORTHY Transcription factor 21 (TCF21) is downregulated in cholangiocarcinoma (CCA) tissues or cells. TCF21 inhibits the growth of xenografts derived from CCA cells. TCF21 suppresses in vivo tumor-associated angiogenesis. TCF21 targets expression and production of proangiogenic factors from CCA cells. The targeting of phosphatidylinositol 3-kinase/protein kinase B and ERK1/2 signaling mediates the anti-angiogenesis of TCF21.

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Prognostic Value and Function of KLF5 in Papillary Thyroid Cancer

Cancers ◽

10.3390/cancers13020185 ◽

2021 ◽

Vol 13 (2) ◽

pp. 185

Author(s):

Poyil Pratheeshkumar ◽

Abdul K. Siraj ◽

Sasidharan Padmaja Divya ◽

Sandeep Kumar Parvathareddy ◽

Sarah Siraj ◽

...

Keyword(s):

Binding Sites ◽

Specific Inhibitor ◽

Papillary Thyroid ◽

Self Renewal ◽

Functional Correlation ◽

Xenograft Growth ◽

Molecular Therapeutic ◽

And Function

The Krüppel-like factor 5 (KLF5), a zinc-finger transcriptional factor, is highly expressed in several solid tumors, but its role in PTC remains unclear. We investigated the expression of KLF5 protein in a large cohort of PTC patient samples and explored its functional role and mechanism in PTC cell lines in vitro and in vivo. KLF5 overexpression was observed in 65.1% of all PTC cases and it was significantly associated with aggressive clinico-pathological parameters and poor outcome. Given the significant association between KLF5 and HIF-1α overexpression in PTC patients, we investigated the functional correlation between KLF5 and HIF-1α in PTC cells. Indeed, the analysis revealed the co-immunoprecipitation of KLF5 with HIF-1α in PTC cells. We also identified KLF5-binding sites in the HIF-1α promoter that specifically bound to KLF5 protein. Mechanistically, KLF5 promoted PTC cell growth, invasion, migration, and angiogenesis, while KLF5 downregulation via specific inhibitor or siRNA reverses its action in vitro. Importantly, the silencing of KLF5 decreases the self-renewal ability of spheroids generated from PTC cells. In addition, the depletion of KLF5 reduces PTC xenograft growth in vivo. These findings suggest KLF5 can be a possible new molecular therapeutic target for a subset of PTC.

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