scholarly journals NAB 2-Expressing Cancer-Associated Fibroblast Promotes HNSCC Progression

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 388 ◽  
Author(s):  
So-Young Choi ◽  
Su Oh ◽  
Soo Kang ◽  
Sung-Min Kang ◽  
Jinkyung Kim ◽  
...  
Keyword(s):  
Lymph Node ◽  
Metastatic Lymph Node ◽  
Xenograft Model ◽  
Matrigel Invasion Assay ◽  
Matrigel Invasion ◽  
Cancer Associated Fibroblast ◽  
Metastatic Lymph ◽  
Mouse Xenograft Model ◽  
Hnscc Patient

Cancer-associated fibroblast (CAF)-specific proteins serve as both prognostic biomarkers and targets for anticancer drugs. In this study, we investigated the role of NGFI-A-binding protein (NAB)2 derived from CAFs in the progression of head and neck squamous cell carcinoma (HNSCC). Patient-derived HNSCC and paired metastatic lymph node tissues were examined for NAB2 expression by immunohistochemistry. Primary CAF cultures were established from HNSCC patient tissue, with paired non-tumor fibroblasts (NTFs) serving as a control. CAF or NTF was used to evaluate the effect of NAB2 on HNSCC progression using FaDu cell spheroids and an in vivo mouse xenograft model. NAB2 was detected in interstitial CAFs in primary and metastatic lymph node tissues of HNSCC patients. NAB2 mRNA and protein levels were higher in CAFs as compared to paired NTFs. Conditioned medium (CM) of NAB2-overexpressing CAFs increased the invasion of FaDu spheroids in the Matrigel invasion assay as compared to CM of NTF. Co-injection of NAB2-overexpressing CAFs with FaDu spheroids into mice enhanced the growth of tumors. These data suggest that NAB2-overexpressing CAFs promotes HNSCC progression and is a potential therapeutic target for preventing HNSCC metastasis.

scholarly journals Oncogenic lncRNA ZNF561-AS1 is essential for colorectal cancer proliferation and survival through regulation of miR-26a-3p/miR-128-5p-SRSF6 axis

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Zizhen Si ◽  
Lei Yu ◽  
Haoyu Jing ◽  
Lun Wu ◽  
Xidi Wang
Keyword(s):  
Colorectal Cancer ◽  
Rna Binding ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Cancer Proliferation ◽  
Mouse Xenograft ◽  
Mouse Xenograft Model

Abstract Background Long non-coding RNAs (lncRNA) are reported to influence colorectal cancer (CRC) progression. Currently, the functions of the lncRNA ZNF561 antisense RNA 1 (ZNF561-AS1) in CRC are unknown. Methods ZNF561-AS1 and SRSF6 expression in CRC patient samples and CRC cell lines was evaluated through TCGA database analysis, western blot along with real-time PCR. SRSF6 expression in CRC cells was also examined upon ZNF561-AS1 depletion or overexpression. Interaction between miR-26a-3p, miR-128-5p, ZNF561-AS1, and SRSF6 was examined by dual luciferase reporter assay, as well as RNA binding protein immunoprecipitation (RIP) assay. Small interfering RNA (siRNA) mediated knockdown experiments were performed to assess the role of ZNF561-AS1 and SRSF6 in the proliferative actives and apoptosis rate of CRC cells. A mouse xenograft model was employed to assess tumor growth upon ZNF561-AS1 knockdown and SRSF6 rescue. Results We find that ZNF561-AS1 and SRSF6 were upregulated in CRC patient tissues. ZNF561-AS1 expression was reduced in tissues from treated CRC patients but upregulated in CRC tissues from relapsed patients. SRSF6 expression was suppressed and enhanced by ZNF561-AS1 depletion and overexpression, respectively. Mechanistically, ZNF561-AS1 regulated SRSF6 expression by sponging miR-26a-3p and miR-128-5p. ZNF561-AS1-miR-26a-3p/miR-128-5p-SRSF6 axis was required for CRC proliferation and survival. ZNF561-AS1 knockdown suppressed CRC cell proliferation and triggered apoptosis. ZNF561-AS1 depletion suppressed the growth of tumors in a model of a nude mouse xenograft. Similar observations were made upon SRSF6 depletion. SRSF6 overexpression reversed the inhibitory activities of ZNF561-AS1 in vivo, as well as in vitro. Conclusion In summary, we find that ZNF561-AS1 promotes CRC progression via the miR-26a-3p/miR-128-5p-SRSF6 axis. This study reveals new perspectives into the role of ZNF561-AS1 in CRC.

scholarly journals LINC00680 enhances hepatocellular carcinoma stemness behavior and chemoresistance by sponging miR-568 to upregulate AKT3

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Gege Shu ◽  
Huizhao Su ◽  
Zhiqian Wang ◽  
Shihui Lai ◽  
Yan Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Mechanism Study ◽  
Downstream Signaling ◽  
Mouse Xenograft Model ◽  
High Level

Abstract Background Hepatocellular carcinoma (HCC) has an extremely poor prognosis due to the development of chemoresistance, coupled with inherently increased stemness properties. Long non-coding RNAs (LncRNAs) are key regulators for tumor cell stemness and chemosensitivity. Currently the relevance between LINC00680 and tumor progression was still largely unknown, with only one study showing its significance in glioblastoma. The study herein was aimed at identifying the role of LINC00680 in the regulation HCC stemness and chemosensitivity. Methods QRT-PCR was used to detect the expression of LINC00680, miR-568 and AKT3 in tissue specimen and cell lines. Gain- or loss-of function assays were applied to access the function of LINC00680 in HCC cells, including cell proliferation and stemness properties. HCC stemness and chemosensitivity were determined by sphere formation, cell viability and colony formation. Luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were performed to examine the interaction between LINC00680 and miR-568 as well as that between miR-568 and AKT3. A nude mouse xenograft model was established for the in vivo study. Results We found that LINC00680 was remarkably upregulated in HCC tissues. Patients with high level of LINC00680 had poorer prognosis. LINC00680 overexpression significantly enhanced HCC cell stemness and decreased in vitro and in vivo chemosensitivity to 5-fluorouracil (5-Fu), whereas LINC00680 knockdown led to opposite results. Mechanism study revealed that LINC00680 regulated HCC stemness and chemosensitivity through sponging miR-568, thereby expediting the expression of AKT3, which further activated its downstream signaling molecules, including mTOR, elF4EBP1, and p70S6K. Conclusion LINC00680 promotes HCC stemness properties and decreases chemosensitivity through sponging miR-568 to activate AKT3, suggesting that LINC00680 might be a potentially important HCC diagnosis marker and therapeutic target.

236 Evaluation of PD-L1 expression in primary lung tumor and metastatic lymph nodes in the presence of immune cells

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A253-A253
Author(s):  
Chris Hansis ◽  
Xiaomei Wang ◽  
Tao Wang ◽  
Gerald Feldman
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Lymph Node ◽  
Tumor Cells ◽  
Squamous Cell ◽  
Immune Cells ◽  
Lymph Node Metastases ◽  
Metastatic Lymph Node ◽  
Metastatic Lymph ◽  
Node Metastases

BackgroundImmunotherapies against programmed death ligand-1 (PD-L1) have been established as an effective treatment for a subset of lung cancer patients. Even though it is critical for a successful therapy to know prevalent PD-L1 expression patterns in all affected tissues, information on matching lymph node metastases and immune cells is particularly limited. The purpose of this study was thus to evaluate comparative PD-L1 expression profiles in those tissues.MethodsFDA-approved IHC assays for PD-L1 (Dako 22C3) were performed on a lung tissue array (LC814A, US Biomax) according to manufacturer’s instructions. Histopathological analysis by H-scoring was performed to determine the rate and intensity of positive tumor and immune cell staining for each of the 80 cores. The H score was calculated as follows: A total of up to 300 cells were assessed, per specimen, at 40x high-power magnification (typically over 7–10 fields). A staining level of 0–3 was then assigned to each cell, to designate the intensity of specific positive membranous-to-cytoplasmic staining. The H score was subsequently calculated as% cells staining at level 1 (x1) +% cells staining at level 2 (x2) +% cells staining at level 3 (x3) = total H score per sample. This resulted in a maximum possible H score of 300.ResultsOf the 16 adenocarcinoma tumor samples with a valid staining, 7 (44%) showed positive PD-L1 staining for tumor cells and 10 (63%) for primary immune cells. Importantly, 9 matching metastatic lymph node samples out of the 16 samples (56%) showed an increased PD-L1 H score compared to primary tumors for both tumor cells and immune cells (figure 1). Of the 15 squamous cell carcinoma samples with a valid staining, 11 (73%) showed detectable PD-L1 expression levels in the primary tumor and 12 (80%) in the primary immune cells, while 7 (47%) and 9 (60%) showed lower scores in matching metastatic lymph node tumor cells and their immune cells, respectively (figure 2). Very low or no expression of PD-L1 was detected in small cell lung cancer, as to be expected from previous studies.Abstract 236 Figure 1PD-L1 Staining in adenocarcinomaAbstract 236 Figure 2PD-L1 Staining in squamous cell carcinomaConclusionsSquamous cell carcinomas and adenocarcinomas display significant heterogeneity with regard to PD-L1 expression in associated lymph node metastases. While the reasons for this frequent discordant PD-L1 expression pattern involving both tumor and immune cells need to be investigated further, our findings may help guide the proper interpretation of PD-L1 companion diagnostic test results and subsequent therapeutic decisions.AcknowledgementsThe views in this Abstract have not been formally disseminated by the U.S. Food and Drug Administration and should not be construed to represent any agency determination or policy.

Automatic FDG-PET-based tumor and metastatic lymph node segmentation in cervical cancer

2014 ◽  
Author(s):  
Dídac R. Arbonès ◽  
Henrik G. Jensen ◽  
Annika Loft ◽  
Per Munck af Rosenschöld ◽  
Anders Elias Hansen ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Lymph Node ◽  
Fdg Pet ◽  
Metastatic Lymph Node ◽  
Metastatic Lymph
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