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Page 14 of 38 J Cancer Metastasis Treat 2020;6:5 I http://dx.doi.org/10.20517/2394-4722.2020.13
7 Laboratory of Nanobiotechnology and Nanotoxicology, Facultad de Ciencias Químicas y Farmacéuticas,
Universidad de Chile, Santiago 1058, Chile.
8 Centro de Biología Celular y Biomedicina (CEBICEM) Campus Los Leones, Universidad San Sebastian,
Santiago 1457, Chile.

Background and aim: Gastric cancer is the fifth most common cancer worldwide. It is mainly diagnosed
via endoscopic examination, which is unsuitable for screening and patient follow-up. A deeper knowledge
of its development and progression can contribute to discovering effective preventive strategies. To
understand this complex process, we focus on microRNAs and exosomes and their metastatic and invasive
potential on gastric cells.

Experimental procedure: We evaluated the expression of several candidate miRNAs in 38 gastric cancer
tissues and 22 plasma samples from gastric cancer patients and compared them to adjacent not-tumor
tissues and plasma from symptomatic patients without cancer, respectively. We performed an association
analysis of the expression of microRNA-335-5p with clinicopathological features and survival curves. For
in vivo study, we injected intravenously microRNA-335-5p-loaded exosomes into immunodeficient mice
with intraperitoneal tumors.

Results: MicroRNA-335-5p is downregulated in advanced gastric cancer (GC) tissues relative to their
paired non-tumor tissues. This downregulation is associated with worse survival rates of patients. We also
demonstrated decreased levels of microRNA-335-5p in total plasma and exosomes isolated from plasma
samples from GC patients, when compared to symptomatic patients without cancer. In our in vivo model
of intraperitoneal carcinogenesis, we observed less metastasis but more necrosis in organs of mice with
microRNA-335-5p-loaded exosomes and all mice lacked ascites.

Conclusion: MicroRNA-335-5p is downregulated in both types of gastric cancer samples. The difference
in expression of this microRNA in plasma of gastric cancer patients versus patients without cancer is so
profound that it can be considered as a possible candidate for non-invasive diagnosis of gastric cancer and
the in vivo results may suggest a therapeutic role for miRNA-335.

20. RANBP9 as potential target in non-small cell lung cancer

Vincenzo Coppola

Department of Cancer Biology and Genetics, Ohio State University & Comprehensive Cancer Center,
Columbus, Ohio 43210, USA.

Non-Small Cell Lung Cancer (NSCLC) is by far the number one cause of cancer related death in the
Western world. Despite the progress made with targeted therapies and immuno-checkpoint inhibitors, the
vast majority of patients still undergo treatment with genotoxic drugs such as platinum-based compounds.
Studies testing whether DNA damaging agents sensitize NSCLC tumors to targeted- or immuno-therapies
are ongoing. However, only a better understanding of the mechanisms of the DNA damage response can
lead to the validation of biomarkers predictive of response to genotoxic agents and the discovery of novel
targets.

We found that overexpression of the scaffold protein Ran Binding Protein 9 (RANBP9) is pervasive
in NSCLC. Most importantly, patients with higher levels of RANBP9 have a worst treatment outcome
[2]
[1]
(Tessari et al. , 2018). Mechanistically, RANBP9 is not only a target (Matsuoka et al. , 2007) but also,