STK35L1 Associates with Nuclear Actin and Regulates Cell Cycle and Migration of Endothelial Cells

Goyal, Pankaj; Behring, Antje; Kumar, Abhishek; Siess, Wolfgang

doi:10.1371/journal.pone.0016249

Cited by 29 publications

(38 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Further, we explored the roles of STK35 on the proliferation of osteosarcoma cells by knocking down its expression. It has been reported that STK35 could regulate cell cycle transition of endothelial cells [10]. Here, an in vitro CCK-8 assay and in vivo xenograft experiments demonstrated that down-regulation of STK35 expression remarkably suppressed the proliferation of osteosarcoma cell lines (Fig.…”

Section: Discussionmentioning

confidence: 61%

See 1 more Smart Citation

Serine/Threonine Kinase 35, a Target Gene of STAT3, Regulates the Proliferation and Apoptosis of Osteosarcoma Cells

Liu

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Serine/threonine kinase 35 (STK35) may be associated with Parkinson disease and human colorectal cancer, but there have been no reports on the expression levels or roles of STK35 in osteosarcoma. Methods: STK35 mRNA expression was determined in osteosarcoma and bone cyst tissues by real-time PCR. Cell proliferation and apoptosis were assessed by Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis, respectively. Results: STK35 was up-regulated in osteosarcoma tissues as indicated by analyzing publicly available expression data (GEO dataset E-MEXP-3628) and real-time PCR analysis on our own cohort. We subsequently investigated the effects of STK35 knockdown on two osteosarcoma cell lines, MG63 and U2OS. STK35 knockdown inhibited the growth of osteosarcoma cells in vitro and in xenograft tumors. Meanwhile, STK35 knockdown enhanced apoptosis. Expression of the active forms and the activity of two major executioner caspases, caspase 3 and caspase 7, were also increased in osteosarcoma cells with STK35 silenced. Additionally, Gene Set Enrichment Analysis (GSEA) identified that the JAK/STAT signaling pathway was positively correlated with STK35 expression. The mRNA expression of STK35 was repressed by STAT3 small interfering RNA (siRNA), but not by siRNA of STAT4, STAT5A or STAT6. A luciferase reporter assay further demonstrated that STAT3 transcriptionally regulated STK35 expression. A chromatin immunoprecipitation (ChIP) assay confirmed the direct recruitment of STAT3 to the STK35 promoter. The promotion effects of STAT3 knockdown on cell apoptosis were partially abolished by STK35 overexpression. Furthermore, STK35 mRNA expression was positively correlated with STAT3 mRNA expression in osteosarcoma tissues by Pearson correlation analysis. Conclusions: These results collectively reveal that STAT3 regulates the transcription of STK35 in osteosarcoma. STK35 may exert an oncogenic role in osteosarcoma.

show abstract

Section: Discussionmentioning

confidence: 61%

“…A few studies have investigated the biological function of STK35. STK35 may regulate CDKN2A expression, G1- to S-phase transition and migration of endothelial cells [10]. Ectopic expression of STK35 enhanced caspase-independent cell death of cells undergoing oxidative stress [11].…”

Section: Introductionmentioning

confidence: 99%

Serine/Threonine Kinase 35, a Target Gene of STAT3, Regulates the Proliferation and Apoptosis of Osteosarcoma Cells

Liu

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…STK35, also known as CLIK1, STK35L1 and listed as one of the top potential targets for miR-377, contains complementary seed sequence in its 3′UTR that is highly conserved among human, chimpanzee, mouse, rat, guinea pig, rabbit, dog, cow, elephant, and horse (Figure 6A). Unlike other cytoplasmic kinases, STK35 is a novel kinase, mainly localized in the nucleus and nucleolus, that binds to nuclear actin (15); thus, it might play a critical role in directly modulating gene transcription machinery (16). A previous study showed that VEGF-stimulation in endothelial cells up-regulates STK35 expression and that STK35 knockdown leads to diminished angiogenic ability of endothelial cells (15).…”

Section: Resultsmentioning

confidence: 99%

“…Additionally, VEGF stimulates STK35 expression in endothelial cells (15). A well-known proangiogenic cytokine, VEGF promotes EPC migration, differentiation, and angiogenic function.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Cardiac Regenerative Ability of Stem Cells After Ischemia-Reperfusion Injury

Joladarashi

Garikipati

Thandavarayan

et al. 2015

Journal of the American College of Cardiology

View full text Add to dashboard Cite

Background Micro ribonucleic acid (miR) dysregulation in the myocardium has been implicated in cardiac remodeling after injury or stress. Objectives This study sought to explore the role of miR in human CD34+ cell (hCD34+) dysfunction in vivo after transplantation into the myocardium under ischemia-reperfusion (I-R) conditions. Methods In response to inflammatory stimuli, the miR array profile of endothelial progenitor cells (EPC) was analyzed using a polymerase chain reaction-based miR microarray. MiR-377 expression was assessed in myocardial tissue from human patients with heart failure (HF). We investigated the effect of miR-377 inhibition on hCD34+ cell angiogenic proteome profile, in vitro and on cardiac repair and function after I-R injury in immunodeficient mice. Results The miR array data from EPCs in response to inflammatory stimuli indicate changes in numerous miR with a robust decrease in miR-377. Human cardiac biopsies from HF patients showed significant increase in miR-377 expression compared to nonfailing control hearts. Proteome profile of hCD34+ cells transfected with miR-377 mimics showed significant decrease in proangiogenic proteins versus nonspecific control transfected cells. We also validated that serine/threonine kinase 35 is a target of miR-377 using a dual-luciferase reporter assay. In a mouse model of myocardial I-R, intramyocardial transplantation of miR-377-silenced hCD34+ cells in immunodeficient mice, promoting neovascularization (at 28 days, post-I-R) and lower interstitial fibrosis, leading to improved left ventricular (LV) function. Conclusions These findings indicate that HF increases miR-377 in the myocardium, which is detrimental to stem cell function, and transplantation of miR-377 knockdown hCD34+ cells into ischemic myocardium promoted their angiogenic ability, attenuating LV remodeling and cardiac fibrosis.

show abstract

“…47 STK35 encodes a serine/threonine protein kinase linking the cell cycle and migration of endothelial cells. 48 While additional studies are warranted to elucidate the biological mechanisms of these genes, these data support the opinion that gene-based approaches may play a key role in identifying novel genetic mechanisms that could be missed by relying on single-marker methods of analysis. 37,49 …”

Section: Discussionmentioning

confidence: 58%

Genome-Wide Linkage and Regional Association Study of Blood Pressure Response to the Cold Pressor Test in Han Chinese

Yang

et al. 2014

Circ Cardiovasc Genet

View full text Add to dashboard Cite

Background Blood pressure (BP) response to cold pressor test (CPT) is associated with increased risk of cardiovascular disease. We performed a genome-wide linkage scan and regional association analysis to identify genetic determinants of BP response to CPT. Methods and Results A total of 1,961 Chinese participants completed the CPT. Multipoint quantitative trait linkage analysis was performed, followed by single-marker and gene-based analyses of variants in promising linkage regions (logarithm of odds, LOD ≥ 2). A suggestive linkage signal was identified for systolic BP (SBP) response to CPT at 20p13-20p12.3, with a maximum multipoint LOD score of 2.37. Based on regional association analysis with 1,351 SNPs in the linkage region, we found that marker rs2326373 at 20p13 was significantly associated with mean arterial pressure (MAP) responses to CPT (P = 8.8×10−6) after FDR adjustment for multiple comparisons. A similar trend was also observed for SBP response (P = 0.03) and DBP response (P = 4.6×10−5). Results of gene-based analyses showed that variants in genes MCM8 and SLC23A2 were associated with SBP response to CPT (P = 4.0×10−5 and 2.7×10−4, respectively), and variants in genes MCM8 and STK35 were associated with MAP response to CPT (P = 1.5×10−5 and 5.0×10−5, respectively). Conclusions Within a suggestive linkage region on chromosome 20, we identified a novel variant associated with BP responses to CPT. We also found gene-based associations of MCM8, SLC23A2 and STK35 in this region. Further work is warranted to confirm these findings. Clinical Trial Registration URL: http://www.clinicaltrials.gov; Unique identifier: NCT00721721.

show abstract

STK35L1 Associates with Nuclear Actin and Regulates Cell Cycle and Migration of Endothelial Cells

Cited by 29 publications

References 48 publications

Serine/Threonine Kinase 35, a Target Gene of STAT3, Regulates the Proliferation and Apoptosis of Osteosarcoma Cells

Serine/Threonine Kinase 35, a Target Gene of STAT3, Regulates the Proliferation and Apoptosis of Osteosarcoma Cells

Enhanced Cardiac Regenerative Ability of Stem Cells After Ischemia-Reperfusion Injury

Genome-Wide Linkage and Regional Association Study of Blood Pressure Response to the Cold Pressor Test in Han Chinese

Contact Info

Product

Resources

About