{"title":"miR-191-3p 靶向的 RGS1 通过抑制 CXCR4/PI3K/AKT 信号抑制了食管癌细胞的干性。","authors":"","doi":"10.1016/j.acthis.2024.152190","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Esophageal cancer is one of the most common malignant tumors in the world. It is urgent to prevent the development and progression of esophageal cancer. Cancer stem cells (CSCs) were reported to have the ability to initiate tumorigenesis, and reducing the stem cell-like characteristics of tumors is an important strategy to inhibit the occurrence and development of tumors. miRNAs are key regulators of the stemness of cancer. Here, we aimed to investigate the role and regulatory mechanism of miR-191-3p in the stemness properties of esophageal cancer cells.</p></div><div><h3>Methods</h3><p>Esophageal cancer cells with stable expression of miR-191-3p were established by lentivirus system. CCK-8 assay, transwell assay<strong>,</strong> wound healing assay were used to evaluate the effect of miR-191-3p on proliferation and metastasis of esophageal cancer cells. The expression of stemness-related markers (NANOG, OCT4, SOX2), ALDH activity, sphere-forming assay and subcutaneous tumor model in nude mice were performed to evaluate the stemness properties of esophageal cancer cells <em>in vitro</em> and <em>in vivo</em>. Dual-luciferase reporter assay was used to verify the molecular mechanism.</p></div><div><h3>Result</h3><p>Here we found that overexpression of miR-191-3p promoted the stemness properties of esophageal cancer cells <em>in vitro</em> and <em>in vivo</em>, including increasing esophageal cancer cell proliferation and metastasis ability, the expression of stemness-related markers NANOG, OCT4, and SOX2, ALDH activity, the number of spheres formed and tumor growth. Bioinformatic analysis and dual-luciferase assay demonstrated that regulator of G protein signaling 1 (RGS1) was the directed target gene of miR-191-3p and attenuated the promotion effect of miR-191-3p on the stemness of esophageal cancer cells. Furthermore, we found that RGS1 knockdown activated the PI3K/AKT pathway by negatively regulating CXCR4 to promote the stemness of esophageal cancer cells.</p></div><div><h3>Conclusions</h3><p>Our findings revealed that RGS1 targeted by miR-191-3p inhibited the stemness of esophageal cancer cells by suppressing the CXCR4/PI3K/AKT pathway, which provide potential prognostic markers and therapeutic targets in the future.</p></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":null,"pages":null},"PeriodicalIF":2.3000,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0065128124000588/pdfft?md5=9a42e6ff9fd33276cd17e59dd8234b62&pid=1-s2.0-S0065128124000588-main.pdf","citationCount":"0","resultStr":"{\"title\":\"RGS1 targeted by miR-191-3p inhibited the stemness properties of esophageal cancer cells by suppressing CXCR4/PI3K/AKT signaling\",\"authors\":\"\",\"doi\":\"10.1016/j.acthis.2024.152190\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Esophageal cancer is one of the most common malignant tumors in the world. It is urgent to prevent the development and progression of esophageal cancer. Cancer stem cells (CSCs) were reported to have the ability to initiate tumorigenesis, and reducing the stem cell-like characteristics of tumors is an important strategy to inhibit the occurrence and development of tumors. miRNAs are key regulators of the stemness of cancer. Here, we aimed to investigate the role and regulatory mechanism of miR-191-3p in the stemness properties of esophageal cancer cells.</p></div><div><h3>Methods</h3><p>Esophageal cancer cells with stable expression of miR-191-3p were established by lentivirus system. CCK-8 assay, transwell assay<strong>,</strong> wound healing assay were used to evaluate the effect of miR-191-3p on proliferation and metastasis of esophageal cancer cells. The expression of stemness-related markers (NANOG, OCT4, SOX2), ALDH activity, sphere-forming assay and subcutaneous tumor model in nude mice were performed to evaluate the stemness properties of esophageal cancer cells <em>in vitro</em> and <em>in vivo</em>. Dual-luciferase reporter assay was used to verify the molecular mechanism.</p></div><div><h3>Result</h3><p>Here we found that overexpression of miR-191-3p promoted the stemness properties of esophageal cancer cells <em>in vitro</em> and <em>in vivo</em>, including increasing esophageal cancer cell proliferation and metastasis ability, the expression of stemness-related markers NANOG, OCT4, and SOX2, ALDH activity, the number of spheres formed and tumor growth. Bioinformatic analysis and dual-luciferase assay demonstrated that regulator of G protein signaling 1 (RGS1) was the directed target gene of miR-191-3p and attenuated the promotion effect of miR-191-3p on the stemness of esophageal cancer cells. Furthermore, we found that RGS1 knockdown activated the PI3K/AKT pathway by negatively regulating CXCR4 to promote the stemness of esophageal cancer cells.</p></div><div><h3>Conclusions</h3><p>Our findings revealed that RGS1 targeted by miR-191-3p inhibited the stemness of esophageal cancer cells by suppressing the CXCR4/PI3K/AKT pathway, which provide potential prognostic markers and therapeutic targets in the future.</p></div>\",\"PeriodicalId\":6961,\"journal\":{\"name\":\"Acta histochemica\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-08-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0065128124000588/pdfft?md5=9a42e6ff9fd33276cd17e59dd8234b62&pid=1-s2.0-S0065128124000588-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta histochemica\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0065128124000588\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta histochemica","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0065128124000588","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
RGS1 targeted by miR-191-3p inhibited the stemness properties of esophageal cancer cells by suppressing CXCR4/PI3K/AKT signaling
Background
Esophageal cancer is one of the most common malignant tumors in the world. It is urgent to prevent the development and progression of esophageal cancer. Cancer stem cells (CSCs) were reported to have the ability to initiate tumorigenesis, and reducing the stem cell-like characteristics of tumors is an important strategy to inhibit the occurrence and development of tumors. miRNAs are key regulators of the stemness of cancer. Here, we aimed to investigate the role and regulatory mechanism of miR-191-3p in the stemness properties of esophageal cancer cells.
Methods
Esophageal cancer cells with stable expression of miR-191-3p were established by lentivirus system. CCK-8 assay, transwell assay, wound healing assay were used to evaluate the effect of miR-191-3p on proliferation and metastasis of esophageal cancer cells. The expression of stemness-related markers (NANOG, OCT4, SOX2), ALDH activity, sphere-forming assay and subcutaneous tumor model in nude mice were performed to evaluate the stemness properties of esophageal cancer cells in vitro and in vivo. Dual-luciferase reporter assay was used to verify the molecular mechanism.
Result
Here we found that overexpression of miR-191-3p promoted the stemness properties of esophageal cancer cells in vitro and in vivo, including increasing esophageal cancer cell proliferation and metastasis ability, the expression of stemness-related markers NANOG, OCT4, and SOX2, ALDH activity, the number of spheres formed and tumor growth. Bioinformatic analysis and dual-luciferase assay demonstrated that regulator of G protein signaling 1 (RGS1) was the directed target gene of miR-191-3p and attenuated the promotion effect of miR-191-3p on the stemness of esophageal cancer cells. Furthermore, we found that RGS1 knockdown activated the PI3K/AKT pathway by negatively regulating CXCR4 to promote the stemness of esophageal cancer cells.
Conclusions
Our findings revealed that RGS1 targeted by miR-191-3p inhibited the stemness of esophageal cancer cells by suppressing the CXCR4/PI3K/AKT pathway, which provide potential prognostic markers and therapeutic targets in the future.
期刊介绍：
Acta histochemica, a journal of structural biochemistry of cells and tissues, publishes original research articles, short communications, reviews, letters to the editor, meeting reports and abstracts of meetings. The aim of the journal is to provide a forum for the cytochemical and histochemical research community in the life sciences, including cell biology, biotechnology, neurobiology, immunobiology, pathology, pharmacology, botany, zoology and environmental and toxicological research. The journal focuses on new developments in cytochemistry and histochemistry and their applications. Manuscripts reporting on studies of living cells and tissues are particularly welcome. Understanding the complexity of cells and tissues, i.e. their biocomplexity and biodiversity, is a major goal of the journal and reports on this topic are especially encouraged. Original research articles, short communications and reviews that report on new developments in cytochemistry and histochemistry are welcomed, especially when molecular biology is combined with the use of advanced microscopical techniques including image analysis and cytometry. Letters to the editor should comment or interpret previously published articles in the journal to trigger scientific discussions. Meeting reports are considered to be very important publications in the journal because they are excellent opportunities to present state-of-the-art overviews of fields in research where the developments are fast and hard to follow. Authors of meeting reports should consult the editors before writing a report. The editorial policy of the editors and the editorial board is rapid publication. Once a manuscript is received by one of the editors, an editorial decision about acceptance, revision or rejection will be taken within a month. It is the aim of the publishers to have a manuscript published within three months after the manuscript has been accepted
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