Background: The aim of the present review is to discuss how the promising field of biobanking can support health care research strategies. As the concept has evolved over time, biobanks have grown from simple biological sample repositories to complex and dynamic units belonging to large infrastructure networks, such as the Pan-European Biobanking and Biomolecular Resources Research Infrastructure (BBMRI). Biobanks were established to support scientific knowledge. Different professional figures with varied expertise collaborate to obtain and collect biological and clinical data from human subjects. At same time biobanks preserve the human and legal rights of each person that offers biomaterial for research.Methods: A literature review was conducted in April 2019 from the online database PubMed, accessed through the Bibliosan platform. Four primary topics related to biobanking will be discussed: (i) evolution, (ii) bioethical issues, (iii) organization, and (iv) imaging.Results: Most biobanks were founded as local units to support specific research projects, so they evolved in a decentralized manner. The consequence is an urgent needing for procedure harmonization regarding sample collection, processing, and storage. Considering the involvement of biomaterials obtained from human beings, different ethical issues such as the informed consent model, sample ownership, veto rights, and biobank sustainability are debated. In the face of these methodological and ethical challenges, international organizations such as BBMRI play a key role in supporting biobanking activities. Finally, a unique development is the creation of imaging biobanks that support the translation of imaging biomarkers (identified using a radiomic approach) into clinical practice by ensuring standardization of data acquisition and analysis, accredited technical validation, and transparent sharing of biological and clinical data.Conclusion: Modern biobanks permit large-scale analysis for individuation of specific diseases biomarkers starting from biological or digital material (i.e., bioimages) with well-annotated clinical and biological data. These features are essential for improving personalized medical approaches, where effective biomarker identification is a critical step for disease diagnosis and prognosis.

MicroRNAs (miRNAs) control cell cycle progression by targeting the transcripts encoding for cyclins, CDKs and CDK inhibitors, such as p27^KIP1 (p27). p27 expression is controlled by multiple transcriptional and posttranscriptional mechanisms, including translational inhibition by miR-221/222 and posttranslational regulation by the SCF^SKP2 complex. The oncosuppressor activity of miR-340 has been recently characterized in breast, colorectal and osteosarcoma tumor cells. However, the mechanisms underlying miR-340-induced cell growth arrest have not been elucidated. Here, we describe miR-340 as a novel tumor suppressor in non-small cell lung cancer (NSCLC). Starting from the observation that the growth-inhibitory and proapoptotic effects of miR-340 correlate with the accumulation of p27 in lung adenocarcinoma and glioblastoma cells, we have analyzed the functional relationship between miR-340 and p27 expression. miR-340 targets three key negative regulators of p27. The miR-340-mediated inhibition of both Pumilio family RNA-binding proteins (PUM1 and PUM2), required for the miR-221/222 interaction with the p27 3′-UTR, antagonizes the miRNA-dependent downregulation of p27. At the same time, miR-340 induces the stabilization of p27 by targeting SKP2, the key posttranslational regulator of p27. Therefore, miR-340 controls p27 at both translational and posttranslational levels. Accordingly, the inhibition of either PUM1 or SKP2 partially recapitulates the miR-340 effect on cell proliferation and apoptosis. In addition to the effect on tumor cell proliferation, miR-340 also inhibits intercellular adhesion and motility in lung cancer cells. These changes correlate with the miR-340-mediated inhibition of previously validated (MET and ROCK1) and potentially novel (RHOA and CDH1) miR-340 target transcripts. Finally, we show that in a small cohort of NSCLC patients (n=23), representative of all four stages of lung cancer, miR-340 expression inversely correlates with clinical staging, thus suggesting that miR-340 downregulation contributes to the disease progression.

Glioblastoma is the most frequent brain tumor in adults and is the most lethal form of human cancer. Despite the improvements in treatments, survival of patients remains poor. In order to identify microRNAs (miRs) involved in glioma tumorigenesis, we evaluated, by a miRarray, differential expression of miRs in the tumorigenic glioma LN-18, LN-229 and U87MG cells compared with the non-tumorigenic T98G cells. Among different miRs we focused our attention on miR-221 and -222. We demonstrated the presence of a binding site for these two miRs in the 3′ untranslated region of the protein tyrosine phosphatase μ (PTPμ). Previous studies indicated that PTPμ suppresses cell migration and is downregulated in glioblastoma. Significantly, we found that miR-221 and -222 overexpression induced a downregulation of PTPμ as analyzed by both western blot and real-time PCR. Furthermore, miR-222 and -221 induced an increase in cell migration and growth in soft agar in glioma cells. Interestingly, the re-expression of PTPμ gene was able to revert the miR-222 and -221 effects on cell migration. Furthermore, we found an inverse correlation between miR-221 and -222 and PTPμ in human glioma cancer samples. In conclusion, our results suggest that miR-221 and -222 regulate glioma tumorigenesis at least in part through the control of PTPμ protein expression.

In the last few years, biomedical research has been boosted by the technological development of analytical instrumentation generating a large volume of data. Such information has increased in complexity from basic (i.e., blood samples) to extensive sets encompassing many aspects of a subject phenotype, and now rapidly extending into genetic and, more recently, radiomic information. Radiogenomics integrates both aspects, investigating the relationship between imaging features and gene expression. From a methodological point of view, radiogenomics takes advantage of non-conventional data analysis techniques that reveal meaningful information for decision-support in cancer diagnosis and treatment. This survey is aimed to review the state-of-the-art techniques employed in radiomics and genomics with special focus on analysis methods based on molecular and multimodal probes. The impact of single and combined techniques will be discussed in light of their suitability in correlation and predictive studies of specific oncologic diseases.

PED/PEA-15 (PED) is a death effector domain family member of 15 kDa with a broad antiapoptotic function found overexpressed in a number of different human tumors, including lung cancer. To date, the mechanisms that regulate PED expression are unknown. Therefore, we address this point by the identification of microRNAs that in non–small cell lung cancer (NSCLC) modulate PED levels. In this work, we identify miR-212 as a negative regulator of PED expression. We also show that ectopic expression of this miR increases tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)–induced cell death in NSCLC cells. In contrast, inhibition of endogenous miR-212 by use of antago-miR results in increase of PED protein expression and resistance to TRAIL treatment. Besides, in NSCLC, we show both in vitro and in vivo that PED and miR-212 expressions are inversely correlated, that is, PED is upregulated and miR-212 is rarely expressed. In conclusion, these findings suggest that miR-212 should be considered as a tumor suppressor because it negatively regulates the antiapoptotic protein PED and regulates TRAIL sensitivity. Cancer Res; 70(9); 3638–46. ©2010 AACR.

Pre–B-cell leukemia homeobox (Pbx)-regulating protein-1 (Prep1) is a ubiquitous homeoprotein involved in early development, genomic stability, insulin sensitivity, and hematopoiesis. Previously we have shown that Prep1 is a haploinsufficient tumor suppressor that inhibits neoplastic transformation by competing with myeloid ecotropic integration site 1 for binding to the common heterodimeric partner Pbx1. Epithelial–mesenchymal transition (EMT) is controlled by complex networks of proinvasive transcription factors responsive to paracrine factors such as TGF-β. Here we show that, in addition to inhibiting primary tumor growth, PREP1 is a novel EMT inducer and prometastatic transcription factor. In human non-small cell lung cancer (NSCLC) cells, PREP1 overexpression is sufficient to trigger EMT, whereas PREP1 down-regulation inhibits the induction of EMT in response to TGF-β. PREP1 modulates the cellular sensitivity to TGF-β by inducing the small mothers against decapentaplegic homolog 3 (SMAD3) nuclear translocation through mechanisms dependent, at least in part, on PREP1-mediated transactivation of a regulatory element in the SMAD3 first intron. Along with the stabilization and accumulation of PBX1, PREP1 induces the expression of multiple activator protein 1 components including the proinvasive Fos-related antigen 1 (FRA-1) oncoprotein. Both FRA-1 and PBX1 are required for the mesenchymal changes triggered by PREP1 in lung tumor cells. Finally, we show that the PREP1-induced mesenchymal transformation correlates with significantly increased lung colonization by cells overexpressing PREP1. Accordingly, we have detected PREP1 accumulation in a large number of human brain metastases of various solid tumors, including NSCLC. These findings point to a novel role of the PREP1 homeoprotein in the control of the TGF-β pathway, EMT, and metastasis in NSCLC. Significance Epithelial–mesenchymal transition (EMT) is a transdifferentiation program implicated in tumor cell dissemination, controlled by networks of transcription complexes responsive to paracrine factors, such as TGF-β. Pre–B-cell leukemia homeobox (Pbx)-regulating protein-1 (PREP1) is a ubiquitous homeodomain transcription factor involved in early development, genomic stability, insulin sensitivity, and hematopoiesis. PREP1 is a haploinsufficient oncosuppressor in mouse tumorigenesis. By characterizing PREP1 as a novel regulator of EMT in human lung adenocarcinoma, we show that PREP1 also harbors prometastatic properties. While autosustaining its activity by stabilizing its transcriptional partner PBX1, PREP1 modulates the responsiveness of lung cancer cells to TGF-β by controlling the expression of two proinvasive transcription factors (SMAD3 and Fos-related antigen 1) implicated in metastasis mechanisms. Thus, PREP1 represents a novel, promising therapeutic target in non-small cell lung cancer.