Suppression of Hepatocellular Carcinoma Progression through FOXM1 and EMT Inhibition via Hydroxygenkwanin-Induced miR-320a Expression

Chou, Li‐Fang; Yang, Wan-Hua; Chen, Chi-Yuan; Chang, Junn-Liang; Leu, Yann Lii; Liou, Miaw‐Jene; Wang, Tong Hong

doi:10.3390/biom10010020

Cited by 29 publications

(24 citation statements)

References 47 publications

(51 reference statements)

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“…In addition, reports have shown that miR-320a is often downregulated in an extended spectrum of cancer types including breast, liver, prostate, lung, and glioma, and is associated with patient survival and tumor stage [ 5 – 9 ]. Mechanistically, miR-320a may inhibit FOXM1 expression, thus suppressing FOXM1-induced epithelial-mesenchymal transition and metastasis [ 10 , 11 ]. miR-320a has also been shown to negatively regulate invasion of tumor cells by blocking HMGB1 or STAT signaling [ 6 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

miR-320a/SP1 negative reciprocal interaction contributes to cell growth and invasion in colorectal cancer

et al. 2021

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Background Transcription factors (TFs) may be engaged in reciprocal regulatory circuits with certain miRNAs to maintain cellular homeostasis. Disequilibrium of the reciprocities by certain tumor-related stimuli may give rise to deregulation of downstream cellular signaling pathways, thus promoting malignant tumor phenotypes. Specificity Protein 1 (SP1) is the most representative member of the tumor-related transcription factors. Previous studies disclosed that SP1 can transcriptionally regulate miRNAs and coding genes to facilitate tumor progression. In our study, we used bioinformatic analysis to predict several SP1-binding sites within the miR-320a promoter and found that SP1 is a predicted target gene of miR-320a. Therefore, we hypothesize a reciprocal regulatory link between SP1 and miR-320a that participates in colorectal cancer (CRC) development Methods We performed bioinformatic analysis, quantitative polymerase chain reaction (qPCR), immunoblotting, dual-luciferase reporter assays, and a series of in vitro and in vivo functional assays to describe a novel SP1/miR-320a reciprocal interaction in CRC Results First, we found that miR-320a was significantly downregulated in CRC tissues and cell lines. Consistent with findings in other cancers, miR-320a exhibited inhibitory effects on cell growth and invasion of CRC in vitro and in vivo. Moreover, we identified SP1 as a target gene of miR-320a, and ectopic SP1 expression partly abolished miR-320a-induced inhibitory effects. Conversely, we confirmed that SP1 interacts with the miR-320a promoter, leading to depression of miR-320a. This illustrates a double-negative feedback loop between miR-320a and SP1. Additionally, based on the fact that SP1 promotes MACC1 transcription, we determined via immunoblotting that the oncogenic MACC1/MET signaling pathway was inactivated in the context of miR-320a-induced SP1 downregulation Conclusion Taken together, our study is the first to describe a miR-320a/SP1 negative reciprocal interaction, which contributes to cell growth and invasion in CRC through modulation of the MACC1/MET signaling pathway.

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Section: Introductionmentioning

confidence: 99%

miR-320a/SP1 negative reciprocal interaction contributes to cell growth and invasion in colorectal cancer

et al. 2021

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“…HGK induced DNA damage, cell cycle arrest, and cell apoptosis in glioma [20]. HGK inhibited cell migration, invasion, and proliferation in oral squamous cell carcinoma and hepatocellular carcinoma [21,22]. These data suggest that HGK is one of the active antitumor flavonoids in the Genkwa Flos extract.…”

Section: Isolation and Identification Of Flavonoids From Genkwa Flosmentioning

confidence: 71%

Hydroxygenkwanin Suppresses Non-Small Cell Lung Cancer Progression by Enhancing EGFR Degradation

Leu

Wang

et al. 2020

Molecules

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Epidermal growth factor receptor (EGFR) is frequently overexpressed and mutated in non-small cell lung cancer (NSCLC), which is the major type of lung cancer. The EGFR tyrosine kinase inhibitors (TKIs) are the approved treatment for patients harboring activating mutations in the EGFR kinase. However, most of the patients treated with EGFR-TKIs developed resistance. Therefore, the development of compounds exhibiting unique antitumor activities might help to improve the management of NSCLC patients. The total flavonoids from Daphne genkwa Sieb. et Zucc. have been shown to contain antitumor activity. Here, we have isolated a novel flavonoid hydroxygenkwanin (HGK) that displays selective cytotoxic effects on all of the NSCLC cells tested. In this study, we employed NSCLC cells harboring EGFR mutations and xenograft mouse model to examine the antitumor activity of HGK on TKI-resistant NSCLC cells. The results showed that HGK suppressed cancer cell viability both in vitro and in vivo. Whole-transcriptome analysis suggests that EGFR is a potential upstream regulator that is involved in the gene expression changes affected by HGK. In support of this analysis, we presented evidence that HGK reduced the level of EGFR and inhibited several EGFR-downstream signalings. These results suggest that the antitumor activity of HGK against TKI-resistant NSCLC cells acts by enhancing the degradation of EGFR.

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“… 10 Chou et al asserted that miR-320a could inhibit the expression of the transcription factor FOXM1 and downstream proteins related to EMT, thereby leading to the suppression of liver cancer cell growth and invasion. 24 Zhang et al reported that miR-320a inhibits endometrial carcinoma cell metastatic capability by preventing TGF-β1-induced EMT. 25 Previous studies also reported that BGN could induce the EMT process of diverse malignancies.…”

Section: Discussionmentioning

confidence: 99%

LINC00460 Promotes Cell Proliferation, Migration, Invasion, and Epithelial-Mesenchymal Transition of Head and Neck Squamous Cell Carcinoma via miR-320a/BGN Axis

Yang¹,

Ru²,

Ling³

et al. 2021

OTT

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Long non-coding RNAs (lncRNAs) play critical roles in cancer onset and development, including head and neck squamous cell carcinoma (HNSCC). This study aimed to investigate the biological role of LINC00460 and the mechanisms underlying epithelialmesenchymal transition (EMT) in HNSCC. Methods: Aberrantly LINC00460 expression in HNSCC and overall survival outcomes were constructed using the TCGA database. Quantitative real-time polymerase chain reaction (RT-qPCR) was applied to examine the LINC00460 expression level in HNSCC cell lines. The role of LINC00460 knockdown on HNSCC cell growth, migration, invasion, and EMT was investigated in vitro using cell counting kit-8 (CCK-8), colony formation, transwell assay, and Western blot assay. Besides, bioinformatics prediction, dual-luciferase reporter assay, and RNA immunoprecipitation (RIP) were performed to reveal the interaction among LINC00460 and its target genes. The function of the LINC00460/miR-320a/BGN axis in HNSCC cells was clarified by rescue assays. Furthermore, the in vivo effects of LINC00460 on tumor growth were investigated using mice xenograft models. Results: In this study, LINC00460 was upregulated in HNSCC tissues and cells and was associated with poor clinical prognosis. Further functional analysis showed that LINC00460 knockdown decreased HNSCC cell proliferation, migration, invasion, as well as EMT in vitro. Mechanistic investigation indicated that LINC00460 sponged miR-320a to upregulate Biglycan (BGN) expression, thereby facilitating HNSCC progression and induced EMT. Moreover, knockdown of LINC00460 significantly suppressed the progression of HNSCC cells in vivo. Conclusion: Taken together, LINC00460 mediates miR-320a/BGN signaling axis to promote cell proliferation, migration, invasion, and induce the EMT process in HNSCC cells. Our findings elucidated a novel mechanism underlying the progression of HNSCC. LINC00460 could serve as a potential therapeutic target for the treatment of HNSCC.

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Suppression of Hepatocellular Carcinoma Progression through FOXM1 and EMT Inhibition via Hydroxygenkwanin-Induced miR-320a Expression

Cited by 29 publications

References 47 publications

miR-320a/SP1 negative reciprocal interaction contributes to cell growth and invasion in colorectal cancer

miR-320a/SP1 negative reciprocal interaction contributes to cell growth and invasion in colorectal cancer

Hydroxygenkwanin Suppresses Non-Small Cell Lung Cancer Progression by Enhancing EGFR Degradation

LINC00460 Promotes Cell Proliferation, Migration, Invasion, and Epithelial-Mesenchymal Transition of Head and Neck Squamous Cell Carcinoma via miR-320a/BGN Axis

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