DataSheet_1_CCDC85A is regulated by miR-224-3p and augments cancer cell resistance to endoplasmic reticulum stress.pdf

MicroRNAs (miRNAs) play pivotal roles in the tumor microenvironment. Here, we analyzed miRNAs in tumor stromal fibroblasts. Expression of miR-224-3p in cancer-associated fibroblasts (CAF) from scirrhous gastric cancer patients was lower than in normal fibroblasts (NF). Introduction of a miR-224-3p mimic attenuated migration and invasion of CAF. Coiled-coil domain containing 85A (CCDC85A), whose function in tumors is not understood, was the target gene of miR-224-3p. Immunohistological analysis revealed that CCDC85A is expressed to varying degrees by cancer cells and CAFs in gastric and pancreatic carcinomas. Downregulation of CCDC85A in cancer cells revealed that these cells are vulnerable to endoplasmic reticulum (ER) stress induced by thapsigargin or tunicamycin, which were ameliorated after addback of CCDC85A. Injection of NF-derived exosomes containing miR-224-3p into the xenograft tumor increased tumor shrinkage by cisplatin treatment. Mechanistically, CCDC85A associated with the molecular chaperone GRP78 and GRP94, thereby inhibiting association of these negative regulators of the unfolded protein response (UPR), leading to sustained activation of PERK and downstream eIF2〈 and ATF4 upon ER stress. These data suggest a novel miR-224-3p-mediated function for CCDC85A: protection from ER stress and cisplatin resistance.</p

Linear expansion of p53-transformed cells in the fallopian tube of mogp-TAg mouse.

<p>In the tubal epithelium of mogp-TAg mouse, multiple linear expansions of p53-positive cells that showed no histological atypia or only subtle atypia were observed. These cells revealed high Ki-67 labelling index. VMN and FLNA expression in the tubal epithelium of mogp-TAg mouse was undetectable for the most part.</p

DataSheet_2_CCDC85A is regulated by miR-224-3p and augments cancer cell resistance to endoplasmic reticulum stress.pdf

MicroRNAs (miRNAs) play pivotal roles in the tumor microenvironment. Here, we analyzed miRNAs in tumor stromal fibroblasts. Expression of miR-224-3p in cancer-associated fibroblasts (CAF) from scirrhous gastric cancer patients was lower than in normal fibroblasts (NF). Introduction of a miR-224-3p mimic attenuated migration and invasion of CAF. Coiled-coil domain containing 85A (CCDC85A), whose function in tumors is not understood, was the target gene of miR-224-3p. Immunohistological analysis revealed that CCDC85A is expressed to varying degrees by cancer cells and CAFs in gastric and pancreatic carcinomas. Downregulation of CCDC85A in cancer cells revealed that these cells are vulnerable to endoplasmic reticulum (ER) stress induced by thapsigargin or tunicamycin, which were ameliorated after addback of CCDC85A. Injection of NF-derived exosomes containing miR-224-3p into the xenograft tumor increased tumor shrinkage by cisplatin treatment. Mechanistically, CCDC85A associated with the molecular chaperone GRP78 and GRP94, thereby inhibiting association of these negative regulators of the unfolded protein response (UPR), leading to sustained activation of PERK and downstream eIF2〈 and ATF4 upon ER stress. These data suggest a novel miR-224-3p-mediated function for CCDC85A: protection from ER stress and cisplatin resistance.</p

Filamin A expression in the human fallopian tube.

<p>A. low-power view, B. high-power view. Filamin A is expressed in smooth muscle bundles of the tubal wall. The immunoreactivity of the epithelium for filamin A is undetectable or only faint in the tubal epithelium.</p

Histological features of serous tubal intraepithelial lesion (STIL).

<p>Two representative STILs (right and left) are shown. STIL on the right is a linear expansion of p53-positive tubal epithelial cells that show no morphological atypia, but increased Ki-67 labelling index (≥10%). STIL on the left consists of p53-positive tubal cells with mild to moderate morphological atypia. It is suspicious for serous tubal intraepithelial carcinoma on morphological basis. However, its Ki-67 labelling index is low (< 10%).</p

Immunofluorescent p53 (green)/VMN (red) double-staining images of the interface between p53 signature and adjacent normal tubal epithelium.

<p>VMN intensities at the interface between p53-positive cells and adjacent p53-negative normal tubal epithelial cells (arrow) and between background tubal epithelial cells (arrowhead) were measured. Graphs on the right show corresponding RVI-Is and RVI-BGs for each image.</p

The diagnostic algorithm of tubal epithelial lesions with p53 alterations.[16,17].

<p>STIC; serous tubal intraepithelial carcinoma, STIL; serous tubal intraepithelial lesion.</p

Clinicopathological features of cases evaluated in this study.

<p>Clinicopathological features of cases evaluated in this study.</p

Relative VMN indices of the interfaces between p53 signatures/STILs and adjacent normal tubal epithelium (RVI-Is).

<p>The average RVI-I was 1.076 (95% CI, 0.9412 – 1.211) for p53 signature and 0.9790 (95% CI, 0.7206 – 1.237) for STIL.</p

Effect of PDT doses on MRSA arthritis. a

<p>: Time course series of bioluminescent images after therapeutic PDT (Th-PDT) in each irradiation energy group. <b>b</b>: A line graph of time courses of bioluminescent intensity after Th-PDT in each irradiation energy group. <b>c</b>: Comparison of the area under the RLU curve (AUC) indicated in b. <i>n</i> = 5 each. *<i>P</i><0.05, **<i>P</i><0.01.</p