Mesenchymal stromal cells (MSCs) can differentiate to various cell types including osteoblasts, chondrocytes, and adipocytes. This cellular flexibility contributes to widespread clinical use of MSCs in tissue repair. However, challenges remain in efficient cellular expansion of MSCs for stem cell therapy. Current MSC culture methods have resulted in reduced self-renewal of MSCs and compromised therapeutic outcomes. This study identifies that nicotinamide mononucleotide (NMN), a key natural NAD⁺ intermediate, effectively encourages MSC expansion in vitro and in vivo. The in vitro expanded MSCs had heightened osteogenesis, but reduced adipogenesis. Furthermore, NMN supplementation stimulated osteogenesis of endogenous MSCs, and protected bone from aging and irradiation induced damage in mice. Mechanistically, we found that NMN treatment upregulated SIRT1. Genetically overexpressing SIRT1 in MSCs by using Prx1 cre; ColA1 ^{flox-stop-flox-SIRT1} mice promoted osteogenesis and reduced adipogenesis in aged mice. Overall, our data demonstrate that NMN promoted MSC self-renewal with strengthened osteogenesis and reduced adipogenesis via upregulating SIRT1 in aged mice.

Chromobox (CBX) proteins are important components of epigenetic regulation complexes known to play key roles in hepatocellular carcinoma (HCC). Little is known about the function of distinct CBXs in HCC. To address this issue, the study investigated the roles of CBXs in the prognosis of HCC using ONCOMINE, UALCAN, Human Protein Atlas, Kaplan-Meier Plotter, c-BioPortal databases. Over expressions of 8 CBXs members were found to be significantly associated with clinical cancer stages and pathological tumor grades in HCC patients. Besides, higher mRNA expressions of CBX1/2/3/6/8 were found to be significantly associated with shorter overall survival (OS) in HCC patients, while higher mRNA expression of CBX7 was associated with favorable OS. Multivariate analysis also showed that high mRNA expressions of CBX1/2/3/6/8 were independent prognostic factors for shorter OS of HCC patients. Moreover, high mutation rate of CBXs (51%) was also observed in HCC patients, and genetic alteration in CBXs was associated with shorter OS and disease-free survival (DFS) in HCC patients. Taken together, these results indicated that CBX1/2/3/6/8 could be prognostic biomarkers for survivals of HCC patients.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Peipei Wang1, 2, *, Song Chen3, *, He Fang4, *, Xiaojuan Wu1, Dabiao Chen1, Liang Peng1, Zhiliang Gao1, 2, Chan Xie1, 2 1Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China 2Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong Province, China 3Department of Radiology, Guangzhou Red Cross Hospital/The Fourth Affiliated Hospital of Jinan University Medical College, Guangzhou, Guangdong Province, China 4Department of Burn Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China *These authors have contributed equally to this work Correspondence to: Chan Xie, e-mail: happyxiechan@hotmail.com Zhiliang Gao, e-mail: gaozl@yahoo.com.cn Keywords: microRNA, human hepatocellular carcinoma, cell cycle Received: July 23, 2015 Accepted: September 30, 2015 Published: October 19, 2015 ABSTRACT Aims: To identify the clinical and functional association of miR-214/199a/199a* cluster in human hepatocellular carcinoma (HCC) and to clarify the mechanism of miR-214. Methods: Kaplan-Meier and Cox proportional regression analyses were used to determine the association of miR-214/199a/199a* cluster levels with the survival of HCC patients. The role of miR-214 in regulating HCC cell proliferation was studied with miR-214 mimics/inhibitor-treated cells. Furthermore, the inhibition effect of miR-214 on E2F2, cyclin-dependent kinase (CDK) 3 and CDK6 expression was assessed in HCC cell lines with miR-214 mimics/inhibitors to increase/decrease miR-214 expression. Direct binding of miR-214 to the 3′-untranslated regions of E2F2, CDK3, and CDK6 was verified by dual-luciferase reporter assay. Results: In analyzing HCC clinical specimens and cell lines, we discovered a uniform decrease in miR-214/199a/199a* expression in comparison with noncancerous tissue or normal liver epithelial cell lines. Higher miR-214 levels were related with improved patient survival. Overexpression of miR-214 in HCC cells inhibited proliferation by inducing G1-S checkpoint arrest. Conversely, RNA interference–mediated silencing of miR-214 promoted cell-cycle progression and accelerated the proliferation of HCC cells. E2F2, CDK3 and CDK6 were each directly targeted for inhibition by miR-214, and restoring their expression reversed miR-214 inhibition of cell-cycle progression. The relationship between expression of miR-214 and its targets was confirmed in HCC tumor xenografts and clinical specimens. Conclusions: Our results demonstrate that miR-214 has tumor-suppressive activity in HCC through inhibition of E2F2, CDK3 and CDK6.