bims-exocan 2023-01-01 papers

Issue of 2023–01–01
five papers selected by
Muhammad Rizwan, COMSATS University

Funct Integr Genomics. 2022 Dec 27. 23(1): 23

Exosomal miRNAs-a diagnostic biomarker acting as a guiding light in the diagnosis of prostate cancer.

Sougata Ghosh Chowdhury, Rachayeeta Ray, Parimal Karmakar.

Prostate cancer, one of the major causes of mortality globally is regarded as the second leading cause of mortality among men. It is known to affect the stromal cells surrounding it. Through the use of exosomes, the affected stromal cells can promote the growth and spread of the cancer. Exosomes are known to play a role not only in the development and progression of cancer but also contribute to the drug-resistance character of cancer cells. Recently, the discovery of the small non-coding RNAs or miRNA has attracted attention of cancer researchers as they can regulate the expression of different genes. Therefore, exosomal miRNA can be used as a novel and reliable biomarker for the diagnosis and treatment of prostate cancer. In addition, exosomal miRNAs can also be used as a potential treatment for prostate cancer. The goal of this review is to provide a comprehensive analysis of the current knowledge about the role of exosomal miRNAs in the treatment of patients with prostate cancer and their potential role in monitoring the disease.

Keywords: Biomarker; Diagnosis; Exosome; Prostate cancer; miRNA

DOI: https://doi.org/10.1007/s10142-022-00951-8

Regen Ther. 2023 Mar;22 19-29

Cancer stem cell-like cells-derived exosomal lncRNA CDKN2B-AS1 promotes biological characteristics in thyroid cancer via miR-122-5p/P4HA1 axis.

Qinghua Wu, Yonggang He, Xin Liu, Fangxiu Luo, Yimei Jiang, Ming Xiang, Ren Zhao.

Introduction: Here, the discussion focused on the function and possible mechanism of cancer stem cell-like cells (CSCs)-derived exosomal CDKN2B-AS1 in thyroid cancer.
Methods: Specifically, the bioinformatics analysis, dual-luciferase reporter assay and RT-qPCR were conducted to obtain the expression and regulation of CDKN2B-AS1, and the downstream miR-122-5p/P4HA1 axis. Exosomes were identified by transmission electron microscopy. The uptake of exosome by recipient cells was observed by PKH67 labeling. Functional experiments and western blot were adopted to detect the effects of exosomal CDKN2B-AS1/miR-122-5p/P4HA1 axis on thyroid cancer cells. Tumor xenograft and in vivo metastasis model combined with RT-qPCR, western blot and hematoxylin-eosin staining verified the role of CDKN2B-AS1.
Results: Exosomal CDKN2B-AS1 up-regulated P4HA1 expression through miR-122-5p. CDKN2B-AS1 and P4HA1 expressions were up-regulated, and miR-122-5p expression was down-regulated in thyroid cancer. Silent CDKN2B-AS1 reduced cell viability and stemness. CDKN2B-AS1 was found to be abundant in CSCs and CSCs-derived exosomes. Exosomal CDKN2B-AS1 silencing could transfer to thyroid cancer cells to elevate E-cadherin level, and diminish P4HA1, N-cadherin and Vimentin levels, thus impeding cell migration and invasion. MiR-122-5p inhibitor reversed the function of exosomal CDKN2B-AS1, while P4HA1 silencing attenuated the effect of miR-122-5p inhibitor. Exosomal CDKN2B-AS1 affected the growth and metastasis of thyroid cancer through the miR-122-5p/P4HA1 axis.
Conclusion: CSCs-derived exosomal CDKN2B-AS1 acts as an oncogene in thyroid cancer through miR-122-5p/P4HA1 axis.

Keywords: CDKN2B-AS1; Cancer stem cell-like cells; Exosomes; Long non-coding RNA; Thyroid cancer

DOI: https://doi.org/10.1016/j.reth.2022.11.005

Eur J Pharm Sci. 2022 Dec 23. pii: S0928-0987(22)00254-8. [Epub ahead of print] 106369

Exosomes derived from lung cancer cells: isolation, characterization, and stability studies.

Monika Ruzycka-Ayoush, Anna M Nowicka, Agata Kowalczyk, Agata Głuchowska, Alicja Targońska, Grażyna Mosieniak, Kamil Sobczak, Mikolaj Donten, Ireneusz P Grudzinski.

Recent advances in nanomedicine have paved the way for developing targeted drug delivery systems. Nanoscale exosomes are present in almost every body fluid and represent a novel mechanism of intercellular communication. Because of their membrane origin, they easily fuse with cells, acting as a natural delivery system and maintaining the bioactivity and immunotolerance of cells. To develop a reconstitutable exosome-based drug candidate for clinical applications, quality assurance by preserving its physical and biological properties during storage is necessary. Therefore, this study aimed to determine the best storage conditions for exosomes derived from lung cancer cells (A549). This study established that the phosphate-buffered saline buffer enriched with 25 mM trehalose is an optimal cryoprotectant for A549-derived exosomes stored at -80°C. Under these conditions, the concentration, size distribution, zeta potential, and total cargo protein levels of the preserved exosomes remained constant.

Keywords: Exosome; lung cancer; preservatives; stability; storage conditions

DOI: https://doi.org/10.1016/j.ejps.2022.106369

Mol Biol Rep. 2022 Dec 30.

Aberrant circulating tumor DNA methylation and exosomal microRNA biomarkers for early detection of colorectal cancer.

Xuchen Zhang, Helei Hou, Man Jiang, Xiaochun Zhang.

INTRODUCTION: Colorectal cancer (CRC) became the third most commonly diagnosed malignancy and the second leading cause of cancer death in 2020. However, the rates of early screening and early diagnosis for CRC remain unsatisfactory. Thus, it is essential to explore the initiating factors of CRC and strategies for its early diagnosis. Research progress in liquid biopsy has led to the finding that circulating tumor-derived DNA (ctDNA) and exosomes play vital roles in early detection of CRC. THE APPLICATIONS OF LIQUID BIOPSY FOR EARLY DETECTION OF COLORECTAL CANCER: Moreover, the increased understanding of epigenetics has highlighted the role of ctDNA methylation in CRC carcinogenesis, and the detection of aberrant ctDNA methylation markers is a feasible strategy for diagnosis of early-stage CRC. Among exosomal markers, microRNAs (miRNAs) are abundant and are the most researched. Upregulated or downregulated expression of exosome-derived miRNAs can indicate the occurrence of early-stage CRC.
FUTURE PERSPECTIVE: The current research progress on aberrant ctDNA methylation and tumor exosomal miRNA biomarkers in early detection of CRC is summarized in this review, and the advantages and shortcomings of the methods are discussed.

Keywords: Circulating tumor DNA; Colorectal cancer; Early detection; Methylation; microRNA

DOI: https://doi.org/10.1007/s11033-022-08194-3

Mol Divers. 2022 Dec 28.

Effect of platelet exosomes loaded with doxorubicin as a targeted therapy on triple-negative breast cancer cells.

Dilara Uslu, Burcin Irem Abas, Gulen Melike Demirbolat, Ozge Cevik.

Exosomes have come to the fore in drug delivery systems due to their biological-based and immune-suppressing properties. In this study, we investigated the effect of doxorubicin loading of exosomes isolated from human platelets on breast cancer.Exosomes released from ADP (1 µM)-activated platelets were isolated by the ultracentrifugation method, and their size and charge were measured with a TEM and zeta sizer. Then doxorubicin (Dox) loading into exosomes (PLT-Exo-Dox) was done by electroporation and incubated with MDA-MB-231 cells. In exosome characterization, CD62 positivity was higher in platelet pellets, while CD9 positivity was higher in released exosomes. The size of PLT-Exo and PLT-Exo-Dox was 82.02 ± 5.21 nm and 116 ± 3.73 nm, with a polydispersity index of 0.26 ± 0.04 and 0.39 ± 0.06, and the Zeta potential was - 16.45 mV and 24.07 mV, respectively. The encapsulation efficiency of the preparation was 86.02 ± 6.16%, with a drug loading capacity of 4.75 ± 0.16 µg/µg of the exosome. In MDA-MB-231 cells, PLT-Exo increased cell viability, while PLT-Exo-Dox decreased in 24 h. The Annexin-V binding level and Bax gene expression were increased in PLT-Exo-Dox and Bcl-2 gene expression was decreased. This study will shed light on the development of release systems that can be effective with chemotherapeutic agents by using exosomes released by cells in the development of personalized treatments.

Keywords: Apoptosis; Cancer therapy; Doxorubicin; Exosome; Personalized nanomedicine; Platelet

DOI: https://doi.org/10.1007/s11030-022-10591-6