Sung-Yup Cho, Wonyoung Kang, Jee Yun Han, Seoyeon Min, Jinjoo Kang, Ahra Lee, Jee Young Kwon, Charles Lee, and Hansoo ParkMol. Cells 2016; 39(2): 77-86 https://doi.org/10.14348/molcells.2016.2350
Abstract : Cancer is a heterogeneous disease caused by diverse genomic alterations in oncogenes and tumor suppressor genes. Despite recent advances in high-throughput sequencing technologies and development of targeted therapies, novel cancer drug development is limited due to the high attrition rate from clinical studies. Patient-derived xenografts (PDX), which are established by the transfer of patient tumors into immunodeficient mice, serve as a platform for co-clinical trials by enabling the integration of clinical data, genomic profiles, and drug responsiveness data to determine precisely targeted therapies. PDX models retain many of the key characteristics of patients’ tumors including histology, genomic signature, cellular heterogeneity, and drug responsiveness. These models can also be applied to the development of biomarkers for drug responsiveness and personalized drug selection. This review summarizes our current knowledge of this field, including methodologic aspects, applications in drug development, challenges and limitations, and utilization for precision cancer medicine.
Bor Luen TangMol. Cells 2016; 39(2): 87-95 https://doi.org/10.14348/molcells.2016.2318
Abstract : Sirt1 is the most prominent and extensively studied member of sirtuins, the family of mammalian class III histone deacetylases heavily implicated in health span and longevity. Although primarily a nuclear protein, Sirt1’s deacetylation of Peroxisome proliferator-activated receptor Gamma Coactivator-1α (PGC-1α) has been extensively implicated in metabolic control and mitochondrial biogenesis, which was proposed to partially underlie Sirt1’s role in caloric restriction and impacts on longevity. The notion of Sirt1’s regulation of PGC-1α activity and its role in mitochondrial biogenesis has, however, been controversial. Interestingly, Sirt1 also appears to be important for the turnover of defective mitochondria by mitophagy. I discuss here evidences for Sirt1’s regulation of mitochondrial biogenesis and turnover, in relation to PGC-1α deacetylation and various aspects of cellular physiology and disease.
Ke Cao, Jingjing Li, Yong Zhao, Qi Wang, Qinghai Zeng, Siqi He, Li Yu, Jianda Zhou, and Peiguo CaoMol. Cells 2016; 39(2): 96-102 https://doi.org/10.14348/molcells.2016.2161
Abstract : miR-101 is considered to play an important role in hepato-cellular carcinoma (HCC), but the underlying molecular mechanism remains to be elucidated. Here, we aimed to confirm whether Girdin is a target gene of miR-101 and determine the tumor suppressor of miR-101 through Girdin pathway. In our previous studies, we firstly found Girdin protein was overexpressed in HCC tissues, and it closely correlated to tumor size, T stage, TNM stage and Edmondson-Steiner stage of HCC patients. After specific small interfering RNA of Girdin was transfected into HepG2 and Huh7.5.1 cells, the proliferation and invasion ability of tumor cells were significantly inhibited. In this study, we further explored the detailed molecular mechanism of Girdin in HCC. Interestingly, we found that miR-101 significantly low-expressed in HCC tissues compared with that in matched normal tissues while Girdin had a relative higher expression, and miR-101 was inversely correlated with Girdin expression. In addition, after miR-101 transfection, the proliferation, migration and invasion abilities of HepG2 cells were weakened. Furthermore, we confirmed that Girdin is a direct target gene of miR-101. Finally we confirmed Talen-mediated Girdin knockout markedly suppressed cell proliferation, migration and invasion in HCC while down-regulation of miR-101 significantly restored the inhibitory effect. Our findings suggested that miR-101/Girdin axis could be a potential application of HCC treatment.
Xianghui Li, Zhilei Zhen, Guodong Tang, Chong Zheng, and Guofu YangMol. Cells 2016; 39(2): 103-110 https://doi.org/10.14348/molcells.2016.2179
Abstract : As a degenerative joint disease, osteoarthritis (OA) constitutes a major cause of disability that seriously affects the quality of life of a large population of people worldwide. However, effective treatment that can successfully reverse OA progression is lacking until now. The present study aimed to determine whether two small non-coding RNAs miR-29a and miR-140, which are significantly down-regulated in OA, can be applied together as potential therapeutic targets for OA treatment. MiRNA synergy score was used to screen the miRNA pairs that potentially synergistically regulate OA. An
Dongwon Baek, Hyun Jin Chun, Songhwa Kang, Gilok Shin, Su Jung Park, Hyewon Hong, Chanmin Kim, Doh Hoon Kim, Sang Yeol Lee, Min Chul Kim, and Dae-Jin YunMol. Cells 2016; 39(2): 111-118 https://doi.org/10.14348/molcells.2016.2188
Md. Ataur Rahman, Kausik Bishayee, and Sung-Oh HuhMol. Cells 2016; 39(2): 119-128 https://doi.org/10.14348/molcells.2016.2232
Yong-Joon Jeon, Jin Hyun Kim, Jong-Il Shin, Mini Jeong, Jaewook Cho, and Kyungho LeeMol. Cells 2016; 39(2): 129-135 https://doi.org/10.14348/molcells.2016.2243
Abstract : Eukaryotic translation initiation factor 2 alpha (eIF2α), which is a component of the eukaryotic translation initiation complex, functions in cell death and survival under various stress conditions. In this study, we investigated the roles of eIF2α phosphorylation in cell death using the breast cancer cell lines MCF-7 and MCF-7/ADR. MCF-7/ADR cells are MCF-7-driven cells that have acquired resistance to doxorubicin (ADR). Treatment of doxorubicin reduced the viability and induced apoptosis in both cell lines, although susceptibility to the drug was very different. Treatment with doxorubicin induced phosphorylation of eIF2α in MCF-7 cells but not in MCF-7/ADR cells. Basal expression levels of Growth Arrest and DNA Damage 34 (GADD34), a regulator of eIF2α, were higher in MCF-7/ADR cells compared to MCF-7 cells. Indeed, treatment with salubrinal, an inhibitor of GADD34, resulted in the upregulation of eIF2α phosphorylation and enhanced doxorubicin-mediated apoptosis in MCF-7/ADR cells. However, MCF-7 cells did not show such synergic effects. These results suggest that dephosphorylation of eIF2α by GADD34 plays an important role in doxorubicin resistance in MCF-7/ADR cells.
Hyuna Noh, and Soochul ParkMol. Cells 2016; 39(2): 136-140 https://doi.org/10.14348/molcells.2016.2245
Abstract : Eph receptors and their ligands, ephrins, mediate cell-to-cell contacts in a specific brain region and their bidirectional signaling is implicated in the regulation of apoptosis during early brain development. In this report, we used the alpha(α)-Cre transgenic line to induce ephrin-A5 over-expression in the distal region of the neural retina. Using this double transgenic embryo, we show that the over-expression of ephrin-A5 was responsible for inducing massive apoptosis in both the nasal and temporal retinas. In addition, the number of differentiated retinal neurons with the exception of the bipolar neuron was significantly reduced, whereas the laminar organization of the mature retina remained intact. Consistent with this finding, an analysis of the mature retina revealed that the size of the whole retina? particularly the nasal and temporal regions?is markedly reduced. These results strongly suggest that the level of ephrin-A5 expression plays a role in the regulation of the size of the retinal progenitor pool in the neural retina.
Hyun A Kim, Ah-Young Shin, Min-Seon Lee, Hee-Jeong Lee, Heung-Ryul Lee, Jongmoon Ahn, Seokhyeon Nahm, Sung-Hwan Jo, Jeong Mee Park, and Suk-Yoon KwonMol. Cells 2016; 39(2): 141-148 https://doi.org/10.14348/molcells.2016.2264
Abstract : Oriental melon (C
Shilpa Rani, Chang Sik Park, Pradeep Kumar Sreenivasaiah, and Do Han KimMol. Cells 2016; 39(2): 149-155 https://doi.org/10.14348/molcells.2016.2284
Abstract : In the heart, excitation-contraction (E-C) coupling is mediated by Ca2+ release from sarcoplasmic reticulum (SR) through the interactions of proteins forming the Ca2+ release unit (CRU). Among them, calsequestrin (CSQ) and histidine-rich Ca2+ binding protein (HRC) are known to bind the charged luminal region of triadin (TRN) and thus directly or indirectly regulate ryanodine receptor 2 (RyR2) activity. However, the mechanisms of CSQ and HRC mediated regulation of RyR2 activity through TRN have remained unclear. We first examined the minimal KEKE motif of TRN involved in the interactions with CSQ2, HRC and RyR2 using TRN deletion mutants and