HPIP silencing inhibits TGF-β1-induced EMT in lung cancer cells

Zhao, Jianjun; Wang, Jing; Mi, Donghui; Ma, Zhongsen

doi:10.3892/ijmm.2017.2851

Cited by 24 publications

(24 citation statements)

References 29 publications

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“…The EMT involves the downregulation of E-cadherin to reinforce LOXL2 upregulates hypoxia-inducible factor-1α signaling through Snail-FBP1 axis in hepatocellular carcinoma cells zHIYONG FAN 1,2 , wEI zHENG 2 , HUI LI 2 , wUJUN wU 2 , XIAOGANG LIU 2 , zHONGJIE SUN 2 , HAITIAN HU 2 , LIXUE DU 2 , QINGAN JIA 1 and QINGGUANG LIU 1 the destabilization of adherens junctions. EMT-related transcription factors, such as Snail, Slug and Twist, can suppress E-cadherin expression (25,26). Snail interacts with H3K9 methyltransferase G9a and DNA methyltransferase Dnmt1 to silence E-cadherin expression.…”

Section: Introductionmentioning

confidence: 99%

LOXL2 upregulates hypoxia‑inducible factor‑1α signaling through Snail‑FBP1 axis in hepatocellular carcinoma cells

Fan

Zheng

et al. 2020

Oncol Rep

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Lysyl oxidase-like 2 (LOXL2), a member of the lysyl oxidase gene family, is involved in the progression of hepatocellular carcinoma progression and metastasis. Increased expression of LOXL2 has been identified in several types of cancer, including hepatocellular carcinoma. Recently, LOXL2 has been reported to promote epithelial-mesenchymal transition by reducing E-cadherin expression via the upregulation of Snail expression. The present study provided evidence demonstrating that LOXL2 inhibited the expression of fructose-1, 6-biphosphatase (FBP1) and enhanced the glycolysis of Huh7 and Hep3B hepatocellular carcinoma cell lines in a Snail-dependent manner. Overexpression of the point-mutated form of LOXL2 [LOXL2(Y689F)], which lacks enzymatic activity, does not affect the expression of Snail1 or FBP1. Notably, targeting extracellular LOXL2 of Huh7 cells with a therapeutic antibody was unable to abolish its regulation on the expression of Snail and FBP1. Knockdown of LOXL2 also interrupted the angiogenesis of Huh7 and Hep3B cells, and this effect could be rescued by the overexpression of Snail. Furthermore, upregulation of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression was observed in Huh7 and Hep3B cells expressing wild-type LOXL2. Notably, the selective LOXL2 inhibitor LOXL2-IN-1 could upregulate the expression of FBP1 and inhibit the expression of Snail, HIF-1α and VEGF in HCC cells, but not in FBP1-knockdown cells. The results of the present study indicated that the intracellular activity of LOXL2 upregulated HIF-1α/VEGF signaling pathways via the Snail-FBP1 axis, and this phenomenon could be inhibited by LOXL2 inhibition. Collectively, these findings further support that LOXL2 exhibits an important role in the progression of hepatocellular carcinoma and implicates LOXL2 as a potential therapeutic agent for the treatment of this disease.

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Section: Introductionmentioning

confidence: 99%

LOXL2 upregulates hypoxia‑inducible factor‑1α signaling through Snail‑FBP1 axis in hepatocellular carcinoma cells

Fan

Zheng

et al. 2020

Oncol Rep

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“…[4][5][6][7][8][9][10][11][12][13][14][15] However, by reviewing the literature, we have not found a report on the expression of HPIP in endometrial cancer. According to the currently reported studies, HPIP exhibited an excessive expression status in numerous cancer tissues, while HPIP expression is involved in various aspects of cancer progression and predicts poor prognosis in cancer patients.…”

Section: Introductionmentioning

confidence: 79%

“…According to the currently reported studies, HPIP exhibited an excessive expression status in numerous cancer tissues, while HPIP expression is involved in various aspects of cancer progression and predicts poor prognosis in cancer patients. [4][5][6][7][8][9][10][11][12][13][14][15] However, by reviewing the literature, we have not found a report on the expression of HPIP in endometrial cancer.…”

Section: Introductionmentioning

confidence: 79%

Overexpression of HPIP as a biomarker for metastasis and prognosis prediction in endometrial cancer patients

Cheng

Zhao

et al. 2019

Clinical Laboratory Analysis

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BackgroundHematopoietic pre‐B‐cell leukemia transcription factor (PBX)‐interacting protein (HPIP) has shown to be overexpressed in several human cancers. The purpose of this study was to explore the expression of HPIP in endometrial cancer (EC) and its associated effects on disease.MethodsA total of 113 EC patients at the Harbin Medical University Cancer Hospital between August 2011 and September 2012 were studied for immunohistochemistry analysis. HPIP expression was detected using real‐time reverse transcription PCR, Western blotting, and immunohistochemistry. Prognostic value of HPIP expression was examined using multivariate Cox regression analysis and Kaplan‐Meier method.ResultsThe result of Western blotting indicated that HPIP protein expression is significantly high in normal tissues compared to EC tissues (P < 0.001). The expression of HPIP was significantly associated with FIGO stage (P < 0.001), histological grade (P < 0.001), depth of myometrial invasion (P < 0.001), and lymph node metastasis (P = 0.033). Kaplan‐Meier analysis demonstrated that there was a significant difference in overall survival and disease‐free survival between the two groups of patients stratified by HPIP expression level (log‐rank, both P = 0.002). Patients with HPIP high expression had significantly shorter median survival time than those with HPIP low expression. Moreover, results of the multivariate analysis revealed that HPIP expression was an independent prognostic factor for predicting overall survival (P = 0.015) and disease‐free survival (P = 0.017) in patients with EC.ConclusionThe present study provides evidence that HPIP predicts EC progression and poor survival, highlighting its potential as a therapeutic target for EC.

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“…It has been previously reported that HPIP is highly expressed in a variety of cancers (32)(33)(34). Recently, Shi et al (35) demonstrated that HPIP silencing suppresses TGF-β1-induced EMT in lung cancer cells by inhibiting activation of mothers against decapentaplegic homolog 2. Similarly, a study conducted by Zhang et al (36) demonstrated that HPIP silencing prevents TGF-β1-induced EMT in ovarian cancer cells.…”

Section: Discussionmentioning

confidence: 99%

miR‑152 regulates TGF‑β1‑induced epithelial‑mesenchymal transition by targeting HPIP in tubular epithelial cells

et al. 2018

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Renal fibrosis is a common pathological feature of chronic kidney diseases, and their development and progression are influenced by epigenetic modifications including aberrant microRNA (miRNA or miR) expression. miRNAs have been demonstrated to modulate the aggressiveness of various cancers and have emerged as possible therapeutic agents for the management of renal fibrosis. Transforming growth factor β1 (TGF‑β1)‑induced epithelial‑mesenchymal transition (EMT) of tubular epithelial cells serves a role in the initiation and progression of renal fibrosis. Furthermore, recent results indicated that the progression of EMT is reversible. The present study aimed to clarify the role of miR‑152 in EMT of the tubular epithelial cell line HK‑2, stimulated by TGF‑β1, using in vitro transfection with a miR‑152 mimic and to further investigate the underlying mechanism of miR‑152 activity. In the present study, miR‑152 expression was significantly reduced in TGF‑β1‑treated HK‑2 cells, accompanied by an increased expression of hematopoietic pre‑B‑cell leukemia transcription factor (PBX)‑interacting protein (HPIP). Additionally, miR‑152 overexpression inhibited TGF‑β1‑induced EMT and suppressed HPIP expression by directly targeting the 3' untranslated region of HPIP in HK‑2 cells. Furthermore, upregulation of HPIP reversed miR‑152‑mediated inhibitory effects on the EMT. Collectively, the results suggest that downregulation of miR‑152 initiates the dedifferentiation of renal tubules and progression of renal fibrosis, which may provide important targets for prevention strategies of renal fibrosis.

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HPIP silencing inhibits TGF-β1-induced EMT in lung cancer cells

Cited by 24 publications

References 29 publications

LOXL2 upregulates hypoxia‑inducible factor‑1α signaling through Snail‑FBP1 axis in hepatocellular carcinoma cells

LOXL2 upregulates hypoxia‑inducible factor‑1α signaling through Snail‑FBP1 axis in hepatocellular carcinoma cells

Overexpression of HPIP as a biomarker for metastasis and prognosis prediction in endometrial cancer patients

miR‑152 regulates TGF‑β1‑induced epithelial‑mesenchymal transition by targeting HPIP in tubular epithelial cells

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