bims-exocan 2024-02-18 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2024‒02‒18
seven papers selected by
Muhammad Rizwan, COMSATS University

Effects of total coumarins from Pileostegia tomentella on exosomal miRNA expression and angiogenesis in colorectal cancer cells.
Exosomal non-coding RNA: A new frontier in diagnosing and treating pancreatic cancer: A review.
Exosome-derived lncRNA A1BG-AS1 attenuates the progression of prostate cancer depending on ZC3H13-mediated m6A modification.
Exosomes secreted by Fusobacterium nucleatum-infected colon cancer cells transmit resistance to oxaliplatin and 5-FU by delivering hsa_circ_0004085.
Bone Marrow Mesenchymal Stem Cell-derived Exosomal microRNA- 99b-5p Promotes Cell Growth of High Glucose-treated Human Umbilical Vein Endothelial Cells by Modulating THAP Domain Containing 2 Expression.
Exosomal miR-122-3p represses the growth and metastasis of MCF-7/ADR cells by targeting GRK4-mediated activation of the Wnt/β-catenin pathway.
Tumorigenic and tumoricidal properties of exosomes in cancers; a forward look.

Pharm Biol. 2024 Dec;62(1): 153-161

Effects of total coumarins from Pileostegia tomentella on exosomal miRNA expression and angiogenesis in colorectal cancer cells.

Ying Liu, Dao-Hai Cheng, Zheng-Ying Su, Ji-Hua Lv, Li Wang, Yu-Yin Deng, Li Li.

  CONTEXT: Pileostegia tomentella Hand. Mazz (Saxifragaceae) total coumarins (TCPT) show antitumour activity in colorectal cancer (CRC) with unknown mechanism of action. Tumour angiogenesis mediated by exosomes-derived miRNA exhibits the vital regulation of endothelial cell function in metastasis of CRC.OBJECTIVE: To investigate the effect of TCPT on exosomal miRNA expression and angiogenesis of CRC cells.
MATERIALS AND METHODS: HT-29-derived exosomes were generated from human CRC cells (HT-29) or either treated with TCPT (100 μg/mL) for 24 h, followed by identification by transmission electron microscope, nanoparticle tracking analysis (NTA) and Western blot. Co-culture experiments for human umbilical vein endothelial cells (HUVECs) and exosomes were performed to detect the uptake of exosomes in HUVECs and its influence on HUVECs cells migration and lumen formation ability. Potential target miRNAs in exosomes were screened out by sequencing technology. Rescue assays of angiogenesis were performed by the transfecting mimics or inhibitors of targeted miRNA into HUVECs.
RESULTS: HT-29-derived exosomes, after TCPT treatment (Exo-TCPT), inhibited the migration and lumen formation of HUVECs, reduced the expression levels of vascular marker (FLT-1, VCAM-1 and VEGFR-2) in HUVECs. Furthermore, the level of miR-375-3p was significantly upregulated in Exo-TCPT. Rescue assays showed that high expression of miR-375-3p in HUVECs inhibited migration and lumen formation abilities, which was consistent with the effects of Exo-TCPT, whereas applying miR-375-3p inhibitors displayed opposite effects.
DISCUSSION AND CONCLUSION: TCPT exhibits anti-angiogenesis in CRC, possibly through upregulating exosomal miR-375-3p. Our findings will shed light on new target exosomes miRNA-mediated tumour microenvironment and the therapeutic application of Pileostegia tomentella in CRC.

Keywords:  Exosome; miR-375-3p; tumour metastasis

DOI:  https://doi.org/10.1080/13880209.2024.2309871
Int J Biol Macromol. 2024 Feb 14. pii: S0141-8130(24)00952-8. [Epub ahead of print] 130149

Exosomal non-coding RNA: A new frontier in diagnosing and treating pancreatic cancer: A review.

Gengyu Sha, Wenjie Zhang, Zhengting Jiang, Daorong Wang, Dong Tang, Qianqian Zhao.

  Pancreatic cancer is the most fatal malignancy worldwide. Once diagnosed, most patients are already at an advanced stage because of their highly heterogeneous, drug-resistant, and metastatic nature and the lack of effective diagnostic markers. Recently, the study of proliferation, metastasis, and drug resistance mechanisms in pancreatic cancer and the search for useful diagnostic markers have posed significant challenges to the scientific community. Exosomes carry various biomolecules (DNA, non-coding RNAs (ncRNAs), proteins, and lipids) that mediate communication between tumors and other cells. ncRNAs can be transported through exosomes to numerous relevant receptor cells and regulate local epithelial-mesenchymal transition (EMT) in tumor tissue, proliferation, drug resistance, and the establishment of pre-metastatic ecological niches in distant organs. In summary, exosomal ncRNAs promote tumor cell proliferation, invasion, and metastasis through multiple EMT, immunosuppression, angiogenesis, and extracellular matrix remodeling pathways. Moreover, we discuss the significant therapeutic significance of exosomal ncRNAs as PC biomarkers.

Keywords:  Diagnosis; Exosomes; Metastasis; Pancreatic cancer; Treatment; ncRNAs

DOI:  https://doi.org/10.1016/j.ijbiomac.2024.130149
Cell Div. 2024 Feb 13. 19(1): 5

Exosome-derived lncRNA A1BG-AS1 attenuates the progression of prostate cancer depending on ZC3H13-mediated m6A modification.

Zhi Yang, Yu Luo, Fan Zhang, Likun Ma.

  BACKGROUND: Exosome-derived long non-coding RNAs (lncRNAs) and N6-methyladenosine (m6A) modifications of lncRNAs have been shown crucial functions in prostate cancer (PCa). Herein, we aim to investigate the detailed mechanism of exosome-derived lncRNA A1BG-AS1 in PCa process.METHODS: PCa cell exosomes were extracted, exosomal marker proteins (CD63, CD9) were detected utilizing western blotting, and exosomes with overexpressing A1BG-AS1 were co-cultured with targeted PCa cells. qRT-PCR was used to detect A1BG-AS1 expression and m6A methyltransferase ZC3H13 in PCa. Transwell, colony formation and CCK-8 assays were utilized to assess the invasion, migration, and proliferation ability of PCa cells. Then, we performed actinomycin D and MeRIP assays to analyze the regulatory effect of ZC3H13 on A1BG-AS1 mRNA stability and m6A modification level.
RESULTS: We observed that A1BG-AS1 and ZC3H13 expression was restricted in PCa tumors. The invasion, proliferation and migratory capacities of PCa cells could be inhibited by up-regulating A1BG-AS1 or by co-culturing with exosomes that up-regulate A1BG-AS1. Additionally, ZC3H13 promoted stable A1BG-AS1 expression by regulating the m6A level of A1BG-AS1.
CONCLUSION: Exosomal A1BG-AS1 was m6A-modified by the m6A methyltransferase ZC3H13 to stabilize expression and thus prevent PCa cell malignancy. These findings offer a possible target for clinical therapy of PCa.

Keywords:  Exosome; Prostate cancer; ZC3H13; lncRNA A1BG-AS1; m6A modification

DOI:  https://doi.org/10.1186/s13008-024-00110-4
J Nanobiotechnology. 2024 Feb 15. 22(1): 62

Exosomes secreted by Fusobacterium nucleatum-infected colon cancer cells transmit resistance to oxaliplatin and 5-FU by delivering hsa_circ_0004085.

Bingqing Hui, Chenchen Zhou, Yetao Xu, Rui Wang, Yuwen Dong, Yirui Zhou, Jie Ding, Xiao Zhang, Jian Xu, Yanhong Gu.

  BACKGROUND: A large number of Fusobacterium nucleatum (Fn) are present in colorectal cancer (CRC) tissues of patients who relapse after chemotherapy, and Fn has been reported to promote oxaliplatin and 5-FU chemoresistance in CRC. Pathogens such as bacteria and parasites stimulate exosome production in tumor cells, and the regulatory mechanism of exosomal circRNA in the transmission of oxaliplatin and 5-FU chemotherapy resistance in Fn-infected CRC remains unclear.METHODS: Hsa_circ_0004085 was screened by second-generation sequencing of CRC tissues. The correlation between hsa_circ_0004085 and patient clinical response to oxaliplatin/5-FU was analyzed. Exosome tracing experiments and live imaging systems were used to test the effect of Fn infection in CRC on the distribution of hsa_circ_0004085. Colony formation, ER tracking analysis and immunofluorescence were carried out to verify the regulatory effect of exosomes produced by Fn-infected CRC cells on chemotherapeutic resistance and ER stress. RNA pulldown, LC-MS/MS analysis and RIP were used to explore the regulatory mechanism of downstream target genes by hsa_circ_0004085.
RESULTS: First, we screened out hsa_circ_0004085 with abnormally high expression in CRC clinical samples infected with Fn and found that patients with high expression of hsa_circ_0004085 in plasma had a poor clinical response to oxaliplatin/5-FU. Subsequently, the circular structure of hsa_circ_0004085 was identified. Fn infection promoted hsa_circ_0004085 formation by hnRNP L and packaged hsa_circ_0004085 into exosomes by hnRNP A1. Exosomes produced by Fn-infected CRC cells transferred hsa_circ_0004085 between cells and delivered oxaliplatin/5-FU resistance to recipient cells by relieving ER stress. Hsa_circ_0004085 enhanced the stability of GRP78 mRNA by binding to RRBP1 and promoted the nuclear translocation of ATF6p50 to relieve ER stress.
CONCLUSIONS: Plasma levels of hsa_circ_0004085 are increased in colon cancer patients with intracellular Fn and are associated with a poor response to oxaliplatin/5-FU. Fn infection promoted hsa_circ_0004085 formation by hnRNP L and packaged hsa_circ_0004085 into exosomes by hnRNP A1. Exosomes secreted by Fn-infected CRC cells deliver hsa_circ_0004085 between cells. Hsa_circ_0004085 relieves ER stress in recipient cells by regulating GRP78 and ATF6p50, thereby delivering resistance to oxaliplatin and 5-FU.

Keywords:  Chemoresistance of colon cancer; Endoplasmic reticulum stress; Exosomes; Fusobacterium nucleatum; hsa_circ_0004085

DOI:  https://doi.org/10.1186/s12951-024-02331-9
Curr Stem Cell Res Ther. 2024 Jan 05.

Bone Marrow Mesenchymal Stem Cell-derived Exosomal microRNA- 99b-5p Promotes Cell Growth of High Glucose-treated Human Umbilical Vein Endothelial Cells by Modulating THAP Domain Containing 2 Expression.

Hongru Ruan, Hui Shi, Wenkang Luan, Sida Pan.

  INTRODUCTION: Bone marrow mesenchymal stem cell-derived exosomes (BMSC-exos) may function as novel candidates for treating diabetic wounds due to their ability to promote angiogenesis.MATERIALS AND METHODS: This study investigated the effects of BMSC-exos on the growth and metastasis of human umbilical vein endothelial cells (HUVECs) treated with high glucose (HG). The exosomes were separated from BMSCs and identified. The cell phenotype was detected by 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and 5-ethynyl-2'-deoxyuridine, wound healing, and transwell assays, while the number of tubes was measured via tube formation assay.
RESULT: The RNA and protein expression levels were studied using reverse transcription-quantitative polymerase chain reaction and western blotting, whereas integration of microRNA-99b-5p (miR-99b-5p) with THAP domain containing 2 (THAP2) was confirmed via dual-luciferase reporter and RNA pull-down assays. Results of transmission electron microscopy, nanoparticle tracking analysis, and laser scanning confocal microscopy revealed that exosomes were successfully separated from BMSCs and endocytosed into the cytoplasm by HUVECs. Similarly, BMSC-exos were found to promote the growth of HG-treated HUVECs, while their growth was inhibited by suppressing miR-99b-5p. THAP2 was found to bind to miR-99b-5p, where THAP2 inhibition reversed the miR-99b-5p-induced effects on cell growth, migration, and tube numbers.
CONCLUSION: In conclusion, miR-99b-5p in BMSC-exo protects HUVECs by negatively regulating THAP2 expression.

Keywords:  Bone marrow mesenchymal stem cell; THAP2; exosomes; human umbilical vein endothelial cell; miR-99b-5p

DOI:  https://doi.org/10.2174/011574888X272011231128073104
Cell Signal. 2024 Feb 14. pii: S0898-6568(24)00069-X. [Epub ahead of print] 111101

Exosomal miR-122-3p represses the growth and metastasis of MCF-7/ADR cells by targeting GRK4-mediated activation of the Wnt/β-catenin pathway.

Binbin Song, Guoxin Hou, Maoyi Xu, Ming Chen.

  Breast cancer (BC) is a common cancer whose incidence continues to grow while its medical progress has stagnated. miRNAs are vital messengers that facilitate communications among different cancer cells. This study was to reveal the correlation of miR-122-3p expression with BC metastasis and Adriamycin (ADM) resistance and its mechanism of inhibiting BC metastasis. We found that expression of miR-122-3p is negatively correlated with BC metastasis and is lower in MCF-7/ADR cells. Overexpression of miR-122-3p in MCF-7/ADR cancer cells impairs their ability to migrate, invade, and stimulate blood vessel formation. Further research found that miR-122-3p directly binds to the 3' UTR of GRK4, reducing the phosphorylation of LRP6, which activates the Wnt/β-catenin signaling pathway, facilitating BC development and metastasis. In addition, we observed that miR-122-3p is present in MCF-7 BCE cells, and treatment of MCF-7/ADR cells with MCF-7-derived exosomes, but not with exosomes from miR-122-3p-deficient MCF-7 cells, has identical effects to miR-122-3p overexpression. Data from xenograft experiments further suggest that excess miR-122-3p and MCF-7-derived exosomes inhibit the growth and metastasis of MCF-7/ADR cancer cells in vivo. In conclusion our data reveal that exosomal miR-122-3p may negatively regulate BC growth and metastasis, potentially serving as a diagnostic and druggable target for BC treatment.

Keywords:  Adriamycin; Breast cancer; Exosome; GRK4; miR-122-3p

DOI:  https://doi.org/10.1016/j.cellsig.2024.111101
Cell Commun Signal. 2024 Feb 15. 22(1): 130

Tumorigenic and tumoricidal properties of exosomes in cancers; a forward look.

Zahra Abbasi-Malati, Seyed Ghader Azizi, Soheil Zamen Milani, Zeinab Aliyari Serej, Narges Mardi, Zahra Amiri, Zohreh Sanaat, Reza Rahbarghazi.

  In recent decades, emerging data have highlighted the critical role of extracellular vesicles (EVs), especially (exosomes) Exos, in the progression and development of several cancer types. These nano-sized vesicles are released by different cell lineages within the cancer niche and maintain a suitable platform for the interchange of various signaling molecules in a paracrine manner. Based on several studies, Exos can transfer oncogenic factors to other cells, and alter the activity of immune cells, and tumor microenvironment, leading to the expansion of tumor cells and metastasis to the remote sites. It has been indicated that the cell-to-cell crosstalk is so complicated and a wide array of factors are involved in this process. How and by which mechanisms Exos can regulate the behavior of tumor cells and non-cancer cells is at the center of debate. Here, we scrutinize the molecular mechanisms involved in the oncogenic behavior of Exos released by different cell lineages of tumor parenchyma. Besides, tumoricidal properties of Exos from various stem cell (SC) types are discussed in detail.

Keywords:  Exosomes; Oncogenic properties; Resistance mechanisms; Stem cells; Tumoricidal effects

DOI:  https://doi.org/10.1186/s12964-024-01510-3