PReD-Bench/PRed-Bench huggingface dataset:
Activation of the Ran GTPase is subject to growth factor regulation and can give rise to cellular transformation
Authors: Richard A Cerione
Jianbin Wang
Thi K Ly
Katherine S Rojas
Kristin F Wilson
Qiyu Feng
Ryan Pereira
Xu Peng
Journal: Journal of Biological Chemistry (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Keywords: GTPase; Ran; growth factor regulation; heregulin; mTOR
Affiliations: Department of Molecular Medicine, Cornell University, Ithaca, New York 14853, USA.

Abstract:  Although the small GTPase Ran is best known for its roles in nucleocytoplasmic transport, mitotic spindle assembly, and nuclear envelope formation, recent studies have demonstrated the overexpression of Ran in multiple tumor types and that its expression is correlated with a poor patient prognosis, providing evidence for the importance of this GTPase in cell growth regulation. Here we show that Ran is subject to growth factor regulation by demonstrating that it is activated in a serum-dependent manner in human breast cancer cells and, in particular, in response to heregulin, a growth factor that activates the Neu/ErbB2 tyrosine kinase. The heregulin-dependent activation of Ran requires mTOR (mammalian target of rapamycin) and stimulates the capped RNA binding capability of the cap-binding complex in the nucleus, thus influencing gene expression at the level of mRNA processing. We further demonstrate that the excessive activation of Ran has important consequences for cell growth by showing that a novel, activated Ran mutant is sufficient to transform NIH-3T3 cells in an mTOR- and epidermal growth factor receptor-dependent manner and that Ran-transformed cells form tumors in mice. 

Retracted: No

PubPeer comments:
 Figure 1G. Splices in 2 panels, but not in the third. ![file] ,
Nemaline myopathy with dilated cardiomyopathy and severe heart failure: A case report
Authors: Qian Wang
Fan Hu
Journal: World Journal of Clinical Cases (2021)
Discipline: CLINICAL MEDICINE
Keywords: Case report; Dilated cardiomyopathy; Heart failure; Myopalladin; Nemaline myopathy
Affiliations: Department of Pediatric Neurology, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China., Department of Pediatric Cardiology, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China. .

Abstract:  Background: Nemaline myopathy (NM) is a rare type of congenital myopathy, with an incidence of 1:50000. Patients with NM often exhibit hypomyotonia and varying degrees of muscle weakness. Skeletal muscles are always affected by this disease, while myocardial involvement is uncommon. However, with improvements in genetic testing technology, it has been found that NM with a mutation in the myopalladin (MYPN) gene not only causes slow, progressive muscle weakness but also results in dilated or hypertrophic cardiomyopathy. Case summary: A 3-year-old pre-school boy was admitted to our hospital with cough, edema, tachypnea, and an increased heart rate. The patient was clinically diagnosed with severe dilated cardiomyopathy and heart failure, and subsequent gene examination confirmed the diagnosis of NM with a mutation in MYPN. Captopril, diuretics, low-dose digoxin, and dobutamine were administered. After 22 d of hospitalization, the patient was discharged due to the improvement of clinical symptoms. During the follow-up period, the patient died of refractory heart failure. Conclusion: Decreased muscular tone and dilated cardiomyopathy are common features of MYPN-mutated NM. Heart transplantation may be a solution to this type of cardiomyopathy. 

Retracted: No

PubPeer comments:
 The authors report a 3-year-old male patient admitted to the hospital for cough, edema, tachypnea, and an increased heart rate. Based on their examinations, they conclude the patient has a form of nemaline myopathy associated with dilated cardiomyopathy caused by a mutation in *MYPN*. My main concerns with the report are: 1. The nemaline myopathy diagnosis has been made without a) performing appropriate histopathological analyses, b) showing the presence of nemaline rods in a muscle biopsy. 2. The report lacks substantial information on the alleged  gene examination performed. Bar from the inclusion of  whole-exome sequencing in the keywords, there is no information on the performed genetic analyses or the causative mutation. A nemaline myopathy diagnosis cannot be made without showing the presence of nemaline rods, a solid NM family history, or a known causative mutation. Unfortunately, this report fails to present any of these. Cardiac involvement in NM is relatively rare, which further presses for substantial proof of genotype-phenotype correlation in this case. The publisher of the journal (Baishideng Publishing Group) is listed on the Stop Predatory Journals list of predatory publishers and was also listed on the original Beall s list of predatory publishers. ,
Knockdown of KCNQ1OT1 attenuates cardiac hypertrophy through modulation of the miR-2054/AKT3 axis
Authors: Fen Li
Yiwei Chen
Wenchuo Zhao
Diqi Zhu
Zhifang Zhang
Journal: Journal of Thoracic Disease (2020)
Discipline: CLINICAL MEDICINE
Keywords: AKT3; KCNQ1OT1; cardiac hypertrophy; miR-2054.
Affiliations: Department of Cardiology, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.

Abstract:  Background: Persistent cardiac hypertrophy threatens health worldwide. Long non-coding RNAs (lncRNAs) attracted lots of attention in cardiac diseases such as cardiac hypertrophy. In this study, we aimed to study the function of KCNQ1OT1 in cardiac hypertrophy. Methods: We first used qRT-PCR to detect the expression of KCNQ1OT1 in Ang-II-induced cardiomyocytes and mouse cardiac hypertrophy models. The function of KCNQ1OT1 was investigated by a loss-of-function test. Analysis of the luciferase reporter gene and RNA pulldown confirmed the interaction between KCNQ1OT1 and miR-2054. The target gene of miR-2054 was predicted by bioinformatics analysis and confirmed by luciferase reporter gene detection. Rescue experiments were performed to evaluate the role of miR-2054/AKT3 in the function of KCNQ1OT1. Results: Our results suggested that KCNQ1OT1 was up-regulated in Ang-II-induced cardiomyocytes and transverse aortic constriction (TAC) mice. Knocking down of KCNQ1OT1 can reduce cell size and downregulate the expression of ANF, BNP and α-MHC in response to Ang-II. KCNQ1OT1 has been shown to compete competitively with miR-2054 and has a negative correlation with its expression. The combination of miR-2054 can reverse the effect of the KCNQ1OT1 combination in Ang-II-induced cardiomyocytes. In addition, AKT3 is a target of miR-2054 and mediates its effect on Ang-II-induced cardiomyocytes. Conclusions: Knockdown of KCNQ1OT1 could attenuate cardiac hypertrophy through modulation of the miR-2054/AKT3 axis. 

Retracted: No

PubPeer comments:
 Fliped images of Ang-II in the Fig. 1A  Bright  column too much similarity with Control than expected. ![file] ,
Decrease of GSK3β Ser-9 Phosphorylation Induced Osteoblast Apoptosis in Rat Osteoarthritis Model
Authors: Yang Liu
Hao Peng
Shuang Deng
Zhi-Gang Nie
Lin-Sheng Long
Sai Xing
Pu-Ji Peng
Journal: Current Medical Science (2019)
Discipline: CLINICAL MEDICINE
Keywords: GSK3β; apoptosis; dexamethasone; osteonecrosis of the femoral head; phosphorylation.
Affiliations: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, 430060, China., Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, 430060, China. .

Abstract:  Nowadays, the cumulative intake of glucocorticoids has become the most common pathogenic factor for non-traumatic osteonecrosis of the femoral head (ONFH). Apoptosis of osteoblasts is considered as the main reason of ONFH at the molecular level. Glycogen synthase kinase 3β (GSK3β) is an important regulator of cellular differentiation and apoptosis pathway, which can modulate the balance between osteoblasts and osteoclasts. Several studies have reported about its function in osteoporosis, but little is known about it in osteonecrosis. In our study, lipopolysaccharide and methylprednisolone were utilized to establish a rat ONFH model. The phosphorylation of GSK3β Ser-9 was decreased in the model. Western blotting examination of β-catenin, Bcl-2, Bax and caspase-3 revealed that the osteoblasts were apoptotic. In dexamethasone (Dex)-incubated primary osteoblasts, the expression profile of GSK3β phosphorylation and apoptotic factors were consistent with those in the rat ONFH model. To further investigate the regulation of osteonecrosis caused by GSK3β, the expression and function of GSK3β were inhibited in Dex-incubated primary osteoblasts. The knockdown of GSK3β by siRNA decreased the expression of Bax and cleaved caspase-3, but increased Bcl-2 and β-catenin. On the other hand, selective inhibition of GSK3β function by LiCl counteracted the activation of caspase-3 induced by Dex. Our work is the first study about the GSK3β phosphorylation in ONFH, and provides evidence for further therapeutic methods. 

Retracted: No

PubPeer comments:
 Figure 1C. * Green boxes: The bottom right corner of Figure 1C appears to show a repetitive element. Could the authors please clarify? It could be something simple as covering up a scale bar or a label. ![file] , 
 #1 ![file] ,