Downregulation of HOXA1 gene affects small cell lung cancer cell survival and chemoresistance under the regulation of miR-100

Xiao, Faman; Bai, Yifeng; Chen, Zhenzhu; Li, Yufa; Luo, Lingaï; Huang, Jie; Yang, Jie; Liao, Hongzhan; Guo, Linlang

doi:10.1016/j.ejca.2014.01.024

Cited by 100 publications

(90 citation statements)

References 39 publications

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“…Similarly, Tang et al (20) identified that HOXA7, HOXA9, HOXA13, HOXB2, HOXB5, HOXB6, HOXB7, HOXB8, HOXB9 and HOXC9 are overexpressed in the carboplatin-resistant small cell lung cancer cell line DMS53. The expression of HOXA1 in small cell lung cancer tissues is associated with chemoresponsiveness; patients with increased expression of HOXA1 are more sensitive to chemotherapy and thus have improved prognoses compared with patients with decreased expression of HOXA1 (16). Consistently, downregulation of HOXA5 expression in breast cancer cells partly blocks apoptosis induced by retinoic acid-like drugs (21).…”

Section: Discussionsupporting

confidence: 55%

“…Numerous studies (15)(16)(17)(18) have also identified the association between HOX genes and chemosensitivity of tumors. A previous study (19) using gene expression profiling revealed that HOX family members, including HOXA9, HOXA10, HOXB13, HOXC4, HOXC10, HOXC11, HOXC13 and HOXD1, are activated in the temozolomide-resistant pediatric glioblastoma cell line KNS42.…”

Section: Discussionmentioning

confidence: 99%

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Increased HOXC6 expression predicts chemotherapy sensitivity in patients with esophageal squamous cell carcinoma

et al. 2017

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Abstract. Increased expression of homeobox C6 (HOXC6) predicts poor prognosis of patients with esophageal squamous cell carcinoma (ESCC) and promotes ESCC cell proliferation. Additionally, the expression of HOXC6 was upregulated in chemosensitive ESCC cell lines. Therefore, it was hypothesized that HOXC6 may be associated with chemosensitivity of ESCC. Patients with ESCC who underwent neoadjuvant chemotherapy followed by surgery by a single-surgeon team between January 2000 and December 2012 were enrolled in the present study. Pretreatment biopsy specimens and postoperative resection samples were collected. Immunohistochemistry was performed to examine HOXC6 expression, and the association between HOXC6 expression and tumor regression grade (TRG) was analyzed. In cell lines exhibiting stable knockdown of HOXC6, Cell Counting Kit-8 assays were used to evaluate the chemosensitivity of cells to various concentrations of cisplatin and paclitaxel. A total of 51 pretreatment biopsy specimens were assessed, and patients with increased expression of HOXC6 in pretreatment biopsy specimens exhibited higher TRGs. A total of 186 surgical samples were evaluated; HOXC6 was expressed at a decreased level in patients with higher TRG and at a high level in patients with lower TRG. In addition, downregulation of HOXC6 decreased the sensitivity of ESCC cell lines to cisplatin and paclitaxel, resulting in an increased half-maximal inhibitory concentration. Increased expression of HOXC6 prior to treatment was associated with chemosensitivity in ESCC tissues.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Increased HOXC6 expression predicts chemotherapy sensitivity in patients with esophageal squamous cell carcinoma

et al. 2017

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“…23 We found that downregulation of HOXA1 gene affects SCLC cell survival and chemoresistance before. 16 In our study, BSP method showed hypermethylation status of HOXA1 CpG islands in the resistant cells as compared with the parental cells. The methylation level of HOXA1 became lower and the expression level was improved remarkably when H69AR and H446AR cells were treated with 5-Aza-CdR.…”

Section: Discussionmentioning

confidence: 94%

“…14 HOXA1 was found to stimulate STAT3 and STAT5B in oncogenic transformation of the immortalized mammary epithelial cells, 15 and regulated the p44/42 MAP kinase pathway in mammary cancer cells. 16 The overexpression of HOXA1 was associated with poor outcome in patients with HCC, whereas the downregulation of HOXA1 can inhibit cell growth, anchorage-independent growth, migration, and invasion of HepG2 cells. 17 In the present study, we first detected the level of lncRNA-HOTAIR in SCLC multidrug resistance cells (H69AR and H446AR) and found the overexpression of HOTAIR in H69AR and H446AR cells.…”

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confidence: 99%

Long noncoding RNA-HOTAIR affects chemoresistance by regulating HOXA1 methylation in small cell lung cancer cells

Fang

Gao

Tong

et al. 2016

Laboratory Investigation

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Homeobox (HOX) transcript antisense RNA (HOTAIR), a long intergenic noncoding RNA (lincRNA), has been reported to play an oncogenic role in various cancers including small cell lung cancer (SCLC). However, it is not known whether HOTAIR can modulate chemoresistance in SCLC. The aim of this study is to investigate the roles of HOTAIR in chemoresistance of SCLC and its possible molecular mechanism. Knockdown of HOTAIR was carried out in SCLC multidrug-resistant cell lines (H69AR and H446AR) and the parental cell lines (H69 and H446) to assess its influence on chemoresistance. The results showed that downregulation of HOTAIR increased cell sensitivity to anticancer drugs through increasing cell apoptosis and cell cycle arrest, and suppressed tumor growth in vivo. Moreover, HOXA1 methylation increased in the resistant cells using bisulfite sequencing PCR. Depletion of HOTAIR reduced HOXA1 methylation by decreasing DNMT1 and DNMT3b expression. The interaction between HOTAIR and HOXA1 was validated by RNA immunoprecipitation. Taken together, our study suggested that HOTAIR mediates chemoresistance of SCLC by regulating HOXA1 methylation and could be utilized as a potential target for new adjuvant therapies against chemoresistance.

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“…Although most studies on this microRNA addressed its expression levels and function in neoplastic disease, [20][21][22] our own interest in miR-100 was based on a previous study from our group, where we used microRNA profiling to identify miR-100 as a potent inhibitor of mTOR-dependent angiogenesis and arteriogenesis in mice. 4 In the present investigation, we use an unbiased genomic screen to identify biological processes modulated by miR-100 overexpression in endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-100 Suppresses Chronic Vascular Inflammation by Stimulation of Endothelial Autophagy

Pankratz

Hohnloser

Bemtgen

et al. 2018

Circulation Research

100

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Many attempts to modulate leukocyte-endothelial interaction to prevent or reduce excessive inflammatory reactions were made in the past. However, the basic regulatory principles of the endothelial inflammatory process remain unclear. It seems that the inhibition of individual components of the inflammatory cascade, for example, by a single antibody against an adhesion molecule, may not be enough to achieve a sustained effect on vascular inflammation.In the past years, microRNAs have been identified as important regulators of gene expression in a wide range of Molecular Medicine© 2017 American Heart Association, Inc. Rationale:The interaction of circulating cells within the vascular wall is a critical event in chronic inflammatory processes, such as atherosclerosis, but the control of the vascular inflammatory state is still largely unclear.Objective: This study was undertaken to characterize the function of the endothelial-enriched microRNA miR-100 during vascular inflammation and atherogenesis. Methods and Results:Based on a transcriptome analysis of endothelial cells after miR-100 overexpression, we identified miR-100 as a potent suppressor of endothelial adhesion molecule expression, resulting in attenuated leukocyte-endothelial interaction in vitro and in vivo as shown by flow cytometry and intravital imaging. Mechanistically, miR-100 directly repressed several components of mammalian target of rapamycin complex 1-signaling, including mammalian target of rapamycin and raptor, which resulted in a stimulation of endothelial autophagy and attenuated nuclear factor κB signaling in vitro and in vivo. In a low-density lipoprotein receptordeficient atherosclerotic mouse model, pharmacological inhibition of miR-100 resulted in enhanced plaque lesion formation and a higher macrophage content of the plaque, whereas a systemic miR-100 replacement therapy had protective effects and attenuated atherogenesis, resulting in a decrease of plaque area by 45%. Finally, analysis of miR-100 expression in >70 samples obtained during carotid endarterectomy revealed that local miR-100 expression was inversely correlated with inflammatory cell content in patients. Conclusions: In summary, we describe an anti-inflammatory function of miR-100 in the vascular response to injury and inflammation and identify an important novel modulator of mammalian target of rapamycin signaling and autophagy

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Downregulation of HOXA1 gene affects small cell lung cancer cell survival and chemoresistance under the regulation of miR-100

Cited by 100 publications

References 39 publications

Increased HOXC6 expression predicts chemotherapy sensitivity in patients with esophageal squamous cell carcinoma

Increased HOXC6 expression predicts chemotherapy sensitivity in patients with esophageal squamous cell carcinoma

Long noncoding RNA-HOTAIR affects chemoresistance by regulating HOXA1 methylation in small cell lung cancer cells

MicroRNA-100 Suppresses Chronic Vascular Inflammation by Stimulation of Endothelial Autophagy

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