Lentivirus-mediated silencing of HSDL2 suppresses cell proliferation in human gliomas

Chen, Ruo-kun; Xue, Yue; Yang, Fengdong; Wei, Xinting; Song, Laijun; Liu, Xianzhi

doi:10.1007/s13277-016-5402-6

Cited by 37 publications

(55 citation statements)

References 25 publications

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“…The production of lentivirus and cell infection was performed as described in previous studies ( Ruokun et al, 2016 ; Song et al, 2016 ). The expression of Zebrafish Calr plasmid was based on the lentivirus vector pCDH-CMV-MCS-EF1-Puro.…”

Section: Methodsmentioning

confidence: 99%

Activation of Nkx2.5–Calr–p53 signaling pathway by hyperglycemia induces cardiac remodeling and dysfunction in adult zebrafish

Sun

Wang

Fang

et al. 2017

Disease Models &Amp; Mechanisms

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Hyperglycemia is an independent risk factor for diabetic cardiomyopathy in humans; however, the underlying mechanisms have not been thoroughly elucidated. Zebrafish (Danio rerio) was used in this study as a novel vertebrate model to explore the signaling pathways of human adult cardiomyopathy. Hyperglycemia was induced by alternately immersing adult zebrafish in a glucose solution or water. The hyperglycemic fish gradually exhibited some hallmarks of cardiomyopathy such as myocardial hypertrophy and apoptosis, myofibril loss, fetal gene reactivation, and severe arrhythmia. Echocardiography of the glucose-treated fish demonstrated diastolic dysfunction at an early stage and systolic dysfunction at a later stage, consistent with what is observed in diabetic patients. Enlarged hearts with decreased myocardial density, accompanied by decompensated cardiac function, indicated that apoptosis was critical in the pathological process. Significant upregulation of the expression of Nkx2.5 and its downstream targets calreticulin (Calr) and p53 was noted in the glucose-treated fish. High-glucose stimulation in vitro evoked marked apoptosis of primary cardiomyocytes, which was rescued by the p53 inhibitor pifithrin-μ. In vitro experiments were performed using compound treatment and genetically via cell infection. Genetically, knockout of Nkx2.5 induced decreased expression of Nkx2.5, Calr and p53. Upregulation of Calr resulted in increased p53 expression, whereas the level of Nkx2.5 remained unchanged. An adult zebrafish model of hyperglycemia-induced cardiomyopathy was successfully established. Hyperglycemia-induced myocardial apoptosis was mediated, at least in part, by activation of the Nkx2.5–Calr–p53 pathway in vivo, resulting in cardiac dysfunction and hyperglycemia-induced cardiomyopathy.

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Section: Methodsmentioning

confidence: 99%

Activation of Nkx2.5–Calr–p53 signaling pathway by hyperglycemia induces cardiac remodeling and dysfunction in adult zebrafish

Sun

Wang

Fang

et al. 2017

Disease Models &Amp; Mechanisms

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“…Results from in vitro experiments disclosed that HSDL2 KD inhibited the growth and metastasis of lung adenocarcinoma. Several previous studies investigating the effects of HSDL2 in other malignant tumors have also confirmed the anti-tumor effects of HSDL2 KD [20][21][22][23]. But unfortunately, the molecular mechanism underlying the role of HSDL2 on tumor progression has not been further explored in these studies.…”

Section: Discussionmentioning

confidence: 94%

“…Studies have shown that the role of HSDL2 in tumor progression is complex and influenced by the type of tumor. HSDL2 has promoting effects on tumor progression in papillary thyroid cancer [20], bladder cancer [21], ovarian cancer [22], and glioma [23], but has suppressing effects in cholangiocarcinoma [24]. At present, the role of HSDL2 in the progression of NSCLC remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Knockdown of HSDL2 inhibits lung adenocarcinoma progression via down-regulating AKT2 expression

et al. 2020

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The aims of the present study are to investigate the role of hydroxysteroid dehydrogenase-like 2 (HSDL2) in the progression of lung adenocarcinoma and illuminate the underlying molecular mechanisms. ShRNA targeting HSDL2 gene (siHSDL2) was utilized to knockdown (KD) HSDL2 expression. In vitro and in vivo experiments were carried out to investigate the effect of siHSDL2 on the progression of lung adenocarcinoma. Microarray hybridization and gene expression analysis were used to investigate effect of siHSDL2 on mRNA expression profile in lung cancer cell line H1299. Our data demonstrated that HSDL2 was up-regulated in lung adenocarcinoma tissue samples (P<0.001). Patients with high HSDL2 expression in cancer tissues had a worse overall survival (P<0.001). HSDL2 KD not only inhibited the proliferation, cell cycle, apoptosis, clone-formation, invasion and migration of lung adenocarcinoma cells in vitro (P<0.05), but also suppressed the growth and metastasis in vivo (P<0.05). HSDL2 KD resulted in up-regulation of 681 genes and down-regulation of 276 genes. HSDL2 KD down-regulated the protein expression and phosphorylation of protein kinase B β (AKT2) (P<0.001 and P<0.001, respectively) and protein expression of baculoviral IAP repeat-containing 3 (BIRC3; P=0.001), and up-regulated the phosphorylation of ERK (P<0.001). Rescue experiments showed that AKT2 overexpression reversed the suppression effect of siHSDL2 on cell proliferation (P<0.001), invasion (P<0.001) and migration (P<0.001) significantly. HSDL2 functions as an oncogene to promote the growth and metastasis of lung adenocarcinoma via promoting the expression of AKT2.

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“…), but HSDL2, IST1 and PABPC1 could also play important roles in KLF5‐mediated tumor growth, which remains to be clarified. For example, silencing the HSDL2 orphan short‐chain dehydrogenase suppresses cell proliferation in glioma, and the polyadenylate binding protein PABPC1 interacts with and stabilizes a lncRNA that appears to promote tumor growth and metastasis of human gallbladder cancer . KLF5 regulates a number of cellular processes, so many potential KLF5‐interacting nuclear proteins provide candidates for further characterization for their interactions with KLF5 to regulate different cellular processes.…”

Section: Discussionmentioning

confidence: 99%

CINP is a novel cofactor of KLF5 required for its role in the promotion of cell proliferation, survival and tumor growth

et al. 2018

Intl Journal of Cancer

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Krüppel‐like factor 5 (KLF5) both suppresses and promotes tumor growth depending on cellular context. The mechanisms underlying tumor promotion could be targetable for therapy. Although a number of transcriptional targets of KLF5 have been identified and implicated in KLF5‐mediated tumor growth, how KLF5 regulates these genes remains to be addressed. Here we performed coimmunoprecipitation (co‐IP) and liquid chromatography–tandem mass spectrometry (LC–MS/MS) in the TSU‐Pr1 bladder cancer cell line, in which KLF5 is shown to promote tumor growth, to identify KLF5‐interacting nuclear proteins that are necessary for KLF5’s tumor promoting function. LC–MS/MS revealed 122 potential KLF5 binding proteins in the nuclear proteins precipitated by the KLF5 antibody, and the top nine candidates included AHNAK, TFAM, HSDL2, HNRNPC, CINP, IST1, FBL, PABPC1 and SNRNP40. SRB assays of these nine proteins indicated that silencing CINP had the most potent inhibitory effect on cell growth in KLF5‐expressing cells but did not affect parental TSU‐Pr1 cells. Further analyses not only confirmed the physical interaction between KLF5 and CINP, also demonstrated that knockdown of CINP attenuated the effects of KLF5 on cell cycle progression, apoptosis and tumorigenesis. Silencing CINP also attenuated the effect of KLF5 on the expression of a number of genes and signaling pathways, including cell cycle regulator Cyclin D1 and apoptosis‐related Caspase 7. These results suggest that CINP is a cofactor of KLF5 that is crucial for the promotion of tumor growth, and that the KLF5‐CINP interaction could be a novel therapeutic target for inhibiting KLF5‐promoted tumor growth.

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Lentivirus-mediated silencing of HSDL2 suppresses cell proliferation in human gliomas

Cited by 37 publications

References 25 publications

Activation of Nkx2.5–Calr–p53 signaling pathway by hyperglycemia induces cardiac remodeling and dysfunction in adult zebrafish

Activation of Nkx2.5–Calr–p53 signaling pathway by hyperglycemia induces cardiac remodeling and dysfunction in adult zebrafish

Knockdown of HSDL2 inhibits lung adenocarcinoma progression via down-regulating AKT2 expression

CINP is a novel cofactor of KLF5 required for its role in the promotion of cell proliferation, survival and tumor growth

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