RAB27A promotes the proliferation and invasion of colorectal cancer cells

Li, Qingyan; Zhao, Huixia; Dong, Wei; Guan, Na; Y, Hu; Zeng, Zhi-Yan; Zhang, He; Zhang, Fengyun; Li, Qiuwen; Yang, Jingwen; Xiao, Wenhua

doi:10.1038/s41598-022-23696-7

Cited by 6 publications

(3 citation statements)

References 45 publications

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“…In some studies, Rab27a is demonstrated to regulate exosome production and metastasis. Disrupting Rab27a expression reduces exosome release, tumor growth, and metastasis in melanoma, pancreatic cancer and colorectal cancer [ 39 – 41 ]. In our study, we demonstrated that miR-124-3p inhibits Rab27a expression via directly targeting its 3′-UTR, which inhibiting the exosome secretion.…”

Section: Discussionmentioning

confidence: 99%

MiR-124-3p impedes the metastasis of non-small cell lung cancer via extracellular exosome transport and intracellular PI3K/AKT signaling

Zhu

Zhang

et al. 2023

Biomark Res

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Background Metastasis is a significant factor that affects the survival of patients with non-small cell lung cancer (NSCLC). Nevertheless, the molecular regulatory mechanism underlying the metastasis is currently not fully understood. This study aims to identify the important role of miR-124-3p in metastasis of NSCLC, thereby providing a potential therapeutic intervention. Methods Exosome secretion was determined by Nanoparticle Tracking Analysis (NTA) and the uptake was measured by fluorescence inverted microscope. The binding mechanism between miR-124-3p and its upstream or downstream target genes was validated experimentally by Luciferase reporter. Cells migration was evaluated by transwell assays. Transcriptome sequencing on A549 was carried out to verify the potential signaling pathway underlying miR-124-3p regulation. Western blotting analysis was used to assess the level of AKT, p-AKT, PI3K, and p-PI3K protein expression in NSCLC cell lines. The role of miR-124-3p to suppress the tumor metastasis was verified in NSCLC xenograft model. Results Exosomes were more abundant in serum from patients with advanced lung cancer (n = 24 patients) than in these from patients with early-stage lung cancer (n = 30 patients), which suggested the potential correlation between amount of exosome secretion and the metastasis of NSCLC. Interestingly, the exosome release, uptake and the migration of NSCLC cells were notably inhibited by miR-124-3p. LINC00511 suppressed the expression of miR-124-3p to facilitate exosome transport due to its role as the competitive endogenous RNA for miR-124-3p. The miR-124-3p could directly target the 3′-UTR of Rab27a in NSCLC cells to inhibit exosome secretion and thereby prevent cell migration and invasion. Aside from the inhibition of exosome transport, miR-124-3p inhibited the activation of PI3K/AKT signaling in the intracellular environment. Finally, by measuring subcutaneous tumor weight and volume and lung metastasis, we also demonstrated that miR-124-3p inhibited tumor growth in vivo. Conclusion In NSCLC, miR-124-3p significantly suppressed metastasis through extracellular exosome transport and intracellular PI3K/AKT signaling. These findings provide new insights toward a better understanding of the NSCLC metastasis and suggest a potential treatment biomarker for NSCLC.

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Section: Discussionmentioning

confidence: 99%

MiR-124-3p impedes the metastasis of non-small cell lung cancer via extracellular exosome transport and intracellular PI3K/AKT signaling

Zhu

Zhang

et al. 2023

Biomark Res

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“…As stated before, Rab-GTPase families are involved in EV release; thus, inhibiting Rab proteins can block EV secretion [ 243 ]. Rab27A knockdown has been illustrated to curtail growth and invasion of CRC cells, while Rab27A overexpression restored this effect [ 244 ]. Sulfisoxazole, a sulfonamide antibacterial, disrupts EVs biogenesis and attenuates exosomal PD-L1 expression by reducing Rab27A in colon cancer cells, thereby synergistically improving anti-PD1 therapy response [ 245 ].…”

Section: Therapeutic Application Of Sevs In Crcmentioning

confidence: 99%

The multifaceted role of extracellular vesicles (EVs) in colorectal cancer: metastasis, immune suppression, therapy resistance, and autophagy crosstalk

Rahmati,

Moeinafshar,

Rezaei

2024

J Transl Med

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Extracellular vesicles (EVs) are lipid bilayer structures released by all cells and widely distributed in all biological fluids. EVs are implicated in diverse physiopathological processes by orchestrating cell–cell communication. Colorectal cancer (CRC) is one of the most common cancers worldwide, with metastasis being the leading cause of mortality in CRC patients. EVs contribute significantly to the advancement and spread of CRC by transferring their cargo, which includes lipids, proteins, RNAs, and DNAs, to neighboring or distant cells. Besides, they can serve as non-invasive diagnostic and prognostic biomarkers for early detection of CRC or be harnessed as effective carriers for delivering therapeutic agents. Autophagy is an essential cellular process that serves to remove damaged proteins and organelles by lysosomal degradation to maintain cellular homeostasis. Autophagy and EV release are coordinately activated in tumor cells and share common factors and regulatory mechanisms. Although the significance of autophagy and EVs in cancer is well established, the exact mechanism of their interplay in tumor development is obscure. This review focuses on examining the specific functions of EVs in various aspects of CRC, including progression, metastasis, immune regulation, and therapy resistance. Further, we overview emerging discoveries relevant to autophagy and EVs crosstalk in CRC.

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“…Generation and release of exosomes involves several Rab GTPase proteins, such as Rab11, Rab27, and Rab35 [17]. Rab27a controls exosome secretion in several types of cancer, increases proliferation and invasion, decreases apoptosis, and results in resistance to the cisplatin therapy [18][19][20]. Previous studies have reported that Rab27a promoted cell proliferative, migratory, invasive, and epithelialmesenchymal transition phenotypes in HCC [21,22].…”

Section: Introductionmentioning

confidence: 99%

Astragaloside IV Suppresses the Effects of Hepatocellular Carcinoma Cells on Proliferation, Angiogenesis, and Invasion in Human Umbilical Vein Endothelial Cells by Controlling Exosomes by Inhibiting Rab27a

Min,

Wang,

2023

Journal of Food Biochemistry

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Hepatocellular carcinoma (HCC) is the third most common cancer worldwide, and invasion and metastasis are the leading causes of death. Astragaloside IV (AS-IV), a kind of traditional Chinese medicine, has been widely used in cancer therapy. Cell Counting Kit-8, tube formation, and Transwell analyses were performed to determine cell proliferation, invasion, and angiogenesis of human umbilical vein endothelial cells (HUVECs) under the treatment of Hep3B or SK-Hep1 cells-derived exosomes or Hep3B or SK-Hep1 cells with or without AS-IV treatment. Then, Rab27a overexpression in Hep3B cells was selected to determine the function of AS-IV on the regulation of cell proliferation, invasion, and angiogenesis of HUVECs. Ultimately, the injection of Hep3B cell-derived exosomes or treatment with AS-IV on nude mice was used to comprehensively investigate AS-IV functions in vivo. Hep3B or SK-Hep1 cells promoted proliferation, invasion, and angiogenesis of HUVECs, which were inhibited by AS-IV therapy. The concentrations of Hep3B and SK-Hep1 cells-derived exosomes were markedly reduced after AS-IV therapy. Meanwhile, Rab27a expression was significantly decreased in SK-Hep1 or Hep3B cells after AS-IV therapy, and it inhibited the effects of AS-IV on Hep3B-induced proliferation, invasion, and angiogenesis of HUVECs. Tumor growth was also suppressed by AS-IV, which was accompanied by the decreased expression levels of Ki67 and CD34. Overall, this study demonstrated that AS-IV inhibits the effects of HCC cell-derived exosomes on proliferation, invasion, and angiogenesis of HUVECs via inhibiting Rab27a expression. Practical Applications. To our knowledge, this is the first study to explore the efficacy of AS-IV against HCC cell-induced proliferation, invasion, and angiogenesis of HUVECs to reveal the underlying mechanism. In this study, CCK-8, Transwell, and tube formation assay detection show that AS-IV has an inhibitory effect on HCC cell-induced proliferation, invasion, and angiogenesis of HUVECs by inhibiting Rab27a, which helps in the development of novel nutraceutical/functional food against HCC progression and thus could improve the quality of life in patients with HCC.

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RAB27A promotes the proliferation and invasion of colorectal cancer cells

Cited by 6 publications

References 45 publications

MiR-124-3p impedes the metastasis of non-small cell lung cancer via extracellular exosome transport and intracellular PI3K/AKT signaling

MiR-124-3p impedes the metastasis of non-small cell lung cancer via extracellular exosome transport and intracellular PI3K/AKT signaling

The multifaceted role of extracellular vesicles (EVs) in colorectal cancer: metastasis, immune suppression, therapy resistance, and autophagy crosstalk

Astragaloside IV Suppresses the Effects of Hepatocellular Carcinoma Cells on Proliferation, Angiogenesis, and Invasion in Human Umbilical Vein Endothelial Cells by Controlling Exosomes by Inhibiting Rab27a

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