MiR‐375/SLC7A11 axis regulates oral squamous cell carcinoma proliferation and invasion

Wu, Yadong; Sun, Xin; Song, Bin; Qiu, Xiaoling; Zhao, Jianjiang

doi:10.1002/cam4.1110

Cited by 101 publications

(60 citation statements)

References 39 publications

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“…Transport system Xc, combination of SLC7A11 and SLC3A2, plays an important role in cell growth and drug resistance of PANC 13,26 . In this study, we found that overexpression of SLC7A11 could significantly promote PANC cell proliferation and migration, which is consistent with the previous studies in other cancers 5 .…”

Section: Discussionsupporting

confidence: 93%

“…MicroRNA (miRNA) is a type of small RNA with about 22 nucleotides in length and widely distributed in eukaryotic cells, characterized with highly conservativity in evolution progress and regulatory functions in cell differentiation, proliferation and apoptosis 3,4 . Studies have shown that miRNA expression is abnormal in tissues of various human tumors, which is significantly different in normal tissues, with distinct tissue specificity that could be used to determine the origin of tumors 5 . Therefore, miRNA plays an important role in differentiation and migration of tumor.…”

Section: Introductionmentioning

confidence: 99%

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MiR-139-5p/SLC7A11 Inhibits the Proliferation and Migration of Pancreatic Carcinoma via PI3K/Akt Signaling Pathway

Qu¹,

Wang²,

Chen³

et al. 2019

Preprint

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Objective: Pancreatic carcinoma (PANC) is one of the important aggressive cancers, with deficiency in effective therapeutics. Studies have unveiled that miR-139-5p expression is significantly downregulated in other types of cancers. However, the functions and mechanisms of miR-139-5p in PANC remain unclear. Methods: Bioinformatic analysis was performed to analyze the differentially expressed genes in the TCGA database. PANC cell line with overexpressed miR-139-5p and Solute Carrier Family 7, Member 11 (SLC7A11) was established, and has been used to detect cell proliferation, migration, invasion and colony formation in PANC. Subsequently, bioinformatic analysis and luciferase assay were performed to confirm that SLC7A11 was a target gene of miR-139-5p. Xenograft mouse model was used to investigate the role of miR-139-5p in PANC tumorigenicity. Results: Through bioinformatic analysis, miR-139-5p was predicted to regulate phosphatidylinositol signaling pathway by targeting SLC7A11. MiR-139-5p was found to be lowly expressed in PANC tissues, while SLC7A11 was highly expressed. Low expression of miR-139-5p and high expression of SLC7A11 were positively associated with poor clinical outcomes. PANC cell proliferation, migration, and invasion could be inhibited by miR-139-5p overexpression and could be promoted by SLC7A11 overexpression. MiR-139-5p could regulate the protein expression level of PI3K and Akt associated with phosphatidylinositol signaling pathway could be by inhibiting the expression of SLC7A11. MiR-139-5p overexpression could suppress PANC tumor growth and the expression of SLC7A11, p-PI3K, p-Akt in tumor tissues. Therefore, the inhibiting effect of miR-139-5p to PANC cell proliferation, invasion and migration, at least, was partly due to its inhibiting effect on SLC7A11 expression. Conclusion: These results demonstrated a novel role of miR-139-5p/SLC7A11 in PANC and provided potential prognostic predictors for PANC patients.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

MiR-139-5p/SLC7A11 Inhibits the Proliferation and Migration of Pancreatic Carcinoma via PI3K/Akt Signaling Pathway

Qu¹,

Wang²,

Chen³

et al. 2019

Preprint

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“…1), which may be related to cell tolerance and the toxicity of impurities. Wu et al reported that miR-375 significantly inhibited OSCC cell viability, proliferation, invasion and migration and induced apoptosis [24]. …”

Section: Discussionmentioning

confidence: 99%

Effects of MiR-375-BMPR2 as a Key Factor Downstream of BMP15/GDF9 on the Smad1/5/8 and Smad2/3 Signaling Pathways

Liu¹,

Yuan²,

Chen³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9), which are secreted by oocytes, are important regulators of follicular growth and development and ovarian function. These two factors can regulate the proliferation and apoptosis of cumulus cells via modulation of the Smad signaling pathway. Studies have shown that BMP15 and GDF9 can affect the level of miR-375, whereas the target gene of miR-375 is BMPR2, the type II receptor of BMP15 and GDF9. However, whether or how the BMP15/ GDF9-miR-375-BMPR2 pathway affects the proliferation and apoptosis of bovine cumulus cells through regulation of the Smad signaling pathway remains unclear. Methods: In this study, cumulus cells were first obtained from cumulus-oocyte complexes (COCs). Appropriate concentrations of BMP15 and GDF9 were added during the in vitro culture process. Cell Counting Kit-8 (CCK-8) analyses and flow cytometry were used to determine the effects of BMP15/GDF9 on bovine cumulus cells proliferation and apoptosis. Subsequently, miR-375 mimics, miR-375 inhibitor and BMPR2 siRNA were synthesized and used for transfection experiments. Western Blot analysis was used to detect changes before and after transfection in the expression levels of the BMP15/GDF9 type I receptors ALK4, ALK5 and ALK6; the phosphorylation levels of Smad2/3 and Smad1/5/8, which are key signaling pathway proteins downstream of BMP15/GDF9; the expression levels of PTX3, HAS2 and PTGS2, which are key genes involved in cumulus cells proliferation; and Bcl2/Bax, which are genes involved in apoptosis. Results: The addition of 100 ng/mL BMP15 or 200 ng/mL GDF9 or the combined addition of 50 ng/mL BMP15 and 100 ng/mL GDF9 effectively inhibited bovine cumulus cell apoptosis and promoted cell proliferation. BMP15/GDF9 negatively regulated miR-375 expression and positively regulated BMPR2 expression. High levels of miR-375 and inhibition of BMPR2 resulted in increased expression of ALK4 and decreased expression of PTX3, HAS2 and PTGS2, whereas miR-375 inhibition resulted in the opposite results. BMP15 and GDF9 significantly activated the levels of p-Smad2/3 and p-Smad1/5/8, whereas miR-375 inhibited the levels of p-Smad2/3 and p-Smad1/5/8 by negatively regulating BMPR2 and also led to apoptosis. Conclusion: BMP15 and GDF9 have synergistic effects and can act through miR-375 to affect the expression levels of type I receptor ALK4 and type II receptor BMPR2 and the activation of Smad signaling pathway, which subsequently affected the proliferation, spread and apoptosis of cumulus cells.

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“…[ 8 9 10 11 12 13 ] MicroRNA-375 (miR-375) has been identified to play a tumor-suppressive role in various types of human cancers including hepatocellular carcinoma, non-small cell lung cancer, esophageal cancer, oral squamous cell carcinoma, gastric cancer, pancreatic cancer, colorectal cancer, and prostate cancer. [ 14 15 16 17 ] However, the biological roles of miR-375 in ccRCC have by far not been clearly elucidated.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-375 Suppresses the Tumor Aggressive Phenotypes of Clear Cell Renal Cell Carcinomas through Regulating YWHAZ

Zhang

Xing

Lai

et al. 2018

Chinese Medical Journal

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Background:MicroRNAs (miRNAs) are key regulators during tumor initiation and progression. MicroRNA-375 (MiR-375) has been proven to play a tumor-suppressive role in various types of human malignancies; however, its biological role in clear cell renal cell carcinoma (ccRCC) remains unclear. The purpose of this study was to explore the biologic role as well as the underlying mechanism of miR-375 in ccRCC progression.Methods:Quantitative polymerase chain reaction (qPCR) was applied to test the expression of miR-375 in tissues and cell lines by t-test. Functional experiments were used to investigate the biological role of miR-375 utilizing a gain-of-function strategy. The target of miR-375 was investigated by bioinformatic analysis and further verified by luciferase reporter assay, qPCR, Western blotting, and functional experiments in vitro.Results:Our study demonstrated that miR-375 was significantly downregulated in ccRCC tissues (cancer vs. normal, 0.804 ± 0.079 vs. 1.784 ± 0.200, t = 5.531 P < 0.0001) and cell lines, and loss of miR-375 expression significantly associated with advanced Fuhrman nuclear grades (Grade III and IV vs. Grade I and II, 1.000 ± 0.099 vs. 1.731 ± 0.189, t = 3.262 P = 0.003). Functional studies demonstrated that miR-375 suppressed ccRCC cell proliferation, migration, and invasion (all P < 0.05 in both 786-O and A498 cell lines). Multiple miRNA target prediction algorithms indicated the well-studied oncogene YWHAZ as a direct target of miR-375, which was further confirmed by the luciferase reporter assay, qPCR, and Western blotting. Moreover, restoration of YWHAZ could rescue the antiproliferation effect of miR-375.Conclusions:The data provide the solid evidence that miR-375 plays a tumor-suppressive role in ccRCC progression, partially through regulating YWHAZ. This study expands the antitumor profile of miR-375, and supports its role as a potential therapeutic target in ccRCC treatment.

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MiR‐375/SLC7A11 axis regulates oral squamous cell carcinoma proliferation and invasion

Cited by 101 publications

References 39 publications

MiR-139-5p/SLC7A11 Inhibits the Proliferation and Migration of Pancreatic Carcinoma via PI3K/Akt Signaling Pathway

MiR-139-5p/SLC7A11 Inhibits the Proliferation and Migration of Pancreatic Carcinoma via PI3K/Akt Signaling Pathway

Effects of MiR-375-BMPR2 as a Key Factor Downstream of BMP15/GDF9 on the Smad1/5/8 and Smad2/3 Signaling Pathways

MicroRNA-375 Suppresses the Tumor Aggressive Phenotypes of Clear Cell Renal Cell Carcinomas through Regulating YWHAZ

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