By comparing the expression profiles of microRNAs (miRNAs) in different hepatocellular carcinoma (HCC) subtypes, we identified miR-140-5p as an HCC-related miRNA. We found that miR-140-5p was significantly decreased in HCC tissues and all of six liver cancer cell lines examined and its expression levels were correlated with multiple nodules, vein invasion, capsular formation, and differentiation, as well as overall and disease-free survival of HCC. We also found that miR-140-5p suppressed HCC cell proliferation and HCC metastasis. Multipathway reporter arrays suggested that miR-140-5p inhibited transforming growth factor b (TGF-b) and mitogen-activated protein kinase / extracellular signal-regulated kinase (MAPK/ERK) signaling. TGFB receptor 1 (TGFBR1) and fibroblast growth factor 9 (FGF9) were then characterized as the direct targets for miR-140-5p after it was found that ectopic miR-140-5p expression suppressed TGFBR1 and FGF9 expression. Silencing TGFBR1 and FGF9 by small interfering RNA (siRNA) resembled the phenotype resulting from ectopic miR-140-5p expression, while overexpression of TGFBR1 and FGF9 attenuated the effect of miR-140-5p on HCC growth and metastasis. Conclusion: These data elucidated a tumor suppressor role for miR-140-5p in HCC development and progression with therapeutic potential. Our correlation studies in clinical HCC samples further suggest that miR-140-5p could be a valuable biomarker for HCC prognosis. (HEPATOLOGY 2013;58:205-217) H epatocellular carcinoma (HCC) is one of the most common human cancers in the world, particularly in China.1 It ranks as the fifth most common malignancy and the second leading cause of cancer death worldwide, resulting in more than 695,900 deaths each year.2,3 Although its mortality decreased along with advances in surgical resection, the long-term prognosis remains unsatisfactory. For example, the 5-year survival rate is only 20% to 30% in HCC patients after surgical resection, mainly due to the high recurrence and metastasis rate. 4,5 It has been generally accepted that the invasive and metastatic potentials of HCC are mostly attributed to the differences of pathological and molecular characteristics. 6 Previously, we found a specific subtype of HCC in which the tumor was only around 5 cm in diameter with a single lesion, but the tumor grew expansively within an intact capsule or pseudocapsule. More important, the tumor possessed unique clinical and pathological characteristics. Therefore, we categorized it as solitary large hepatocellular carcinoma (SLHCC) and divided HCC into three different subtypes: SLHCC, nodular HCC (NHCC, node number !2), and small HCC (SHCC, tumor 5 cm). Further study confirmed that the metastatic potential of SLHCC was comparable to SHCC, but significantly less than NHCC.5 Additionally, SLHCC exhibited a similar long-term overall and disease-free survival to Abbreviations: FGF9, fibroblast growth factor 9; HCC, hepatocellular carcinoma; NHCC, nodular hepatocellular carcinoma; qRT-PCR, real-time quantitative PCR; SHCC, small ...

Highlights d First deep proteogenomic landscape of non-smoking lung adenocarcinoma in East Asia d Identified age, sex-related endogenous, and environmental carcinogen mutagenic processes d Proteome-informed classification distinguished clinical features within early stages d Protein networks identified tumorigenesis hallmarks, biomarkers, and druggable targets

miRNA globally deregulates human carcinoma. A critical open question is how many miRNAs functionally participate in cancer development, particularly in metastasis. We systematically evaluate the capability of all known human miRNAs to regulate certain metastasis-relevant cell behaviours. To perform the high-throughput screen of miRNAs, which regulate cell migration, we developed a novel self-assembled cell microarray. Here we show that over 20 % of miRNAs have migratory regulation activity in diverse cell types, indicating a general involvement of miRNAs in migratory regulation. MiR-23b, which is downregulated in human colon cancer samples, potently mediates the multiple steps of metastasis, including tumour growth, invasion and angiogenesis in vivo . It regulates a cohort of prometastatic targets, including FZD7 or MAP3k1 . These fi ndings provide new insight into the physiological and potential therapeutic importance of miRNAs as a new class of functional modulators.

Exosomes are extracellular membranous nanovesicles that mediate local and systemic intercellular communication by transporting proteins or nucleic acids (DNA and RNA) into target cells, thus altering the behaviors of recipient cells. Recent studies have revealed that these vesicles play a critical role in many biological functions, such as cell proliferation, immune regulation, nerve regeneration, and cancer. Adiposederived stem cells (ADSCs) are now considered a multipotent and abundant tool in the field of cell therapy and regenerative medicine. ADSCs can produce and secrete many exosomes, which inherit multiple functions of cells. Therefore, in this review, we will introduce the characteristics of exosomes derived from ADSCs (ADSC-Exos), describe their functions in different biological processes, summarize the latest research achievements, describe their limitations in cell-free therapy, and provide further insights into their clinical application potential for the treatment of certain diseases.

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