bims-exocan 2024-06-30 papers

Issue of 2024–06–30
five papers selected by
Muhammad Rizwan, COMSATS University

Front Endocrinol (Lausanne). 2024 ;15 1337226

Exosomal noncoding RNAs: decoding their role in thyroid cancer progression.

Weiming Sun, Chenjun Jiang, Qianqian Liu, Na Wang, Runchun Huang, Gengchen Jiang, Yuxuan Yang.

Exosomes, as pivotal entities within the tumor microenvironment, orchestrate intercellular communication through the transfer of diverse molecules, among which non-coding RNAs (ncRNAs) such as miRNAs, lncRNAs, and circRNAs play a crucial role. These ncRNAs, endowed with regulatory functions, are selectively incorporated into exosomes. Emerging evidence underscores the significance of exosomal ncRNAs in modulating key oncogenic processes in thyroid cancer (TC), including proliferation, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and immunoediting. The unique composition of exosomes shields their cargo from enzymatic and chemical degradation, ensuring their integrity and facilitating their specific expression in plasma. This positions exosomal ncRNAs as promising candidates for novel diagnostic and prognostic biomarkers in TC. Moreover, the potential of exosomes in the therapeutic landscape of TC is increasingly recognized. This review aims to elucidate the intricate relationship between exosomal ncRNAs and TC, fostering a deeper comprehension of their mechanistic involvement. By doing so, it endeavors to propel forward the exploration of exosomal ncRNAs in TC, ultimately paving the way for innovative diagnostic and therapeutic strategies predicated on exosomes and their ncRNA content.

Keywords: circRNAs; exosomes; lncRNAs; miRNAs; noncoding RNAs; thyroid cancer

DOI: https://doi.org/10.3389/fendo.2024.1337226

Biomed Pharmacother. 2024 Jun 25. pii: S0753-3322(24)00911-9. [Epub ahead of print]177 117027

New insights into the potential of exosomal circular RNAs in mediating cancer chemotherapy resistance and their clinical applications.

Qiang Li, Yuhao Zhang, Peikan Jin, Yepeng Chen, Chuchu Zhang, Xiuchao Geng, Kein Seong Mun, Kean Chang Phang.

Chemotherapy resistance typically leads to tumour recurrence and is a major obstacle to cancer treatment. Increasing numbers of circular RNAs (circRNAs) have been confirmed to be abnormally expressed in various tumours, where they participate in the malignant progression of tumours, and play important roles in regulating the sensitivity of tumours to chemotherapy drugs. As exosomes mediate intercellular communication, they are rich in circRNAs and exhibit a specific RNA cargo sorting mechanism. By carrying and delivering circRNAs, exosomes can promote the efflux of chemotherapeutic drugs and reduce intracellular drug concentrations in recipient cells, thus affecting the cell cycle, apoptosis, autophagy, angiogenesis, invasion and migration. The mechanisms that affect the phenotype of tumour stem cells, epithelial-mesenchymal transformation and DNA damage repair also mediate chemotherapy resistance in many tumours. Exosomal circRNAs are diagnostic biomarkers and potential therapeutic targets for reversing chemotherapy resistance in tumours. Currently, the rise of new fields, such as machine learning and artificial intelligence, and new technologies such as biosensors, multimolecular diagnostic systems and platforms based on circRNAs, as well as the application of exosome-based vaccines, has provided novel ideas for precision cancer treatment. In this review, the recent progress in understanding how exosomal circRNAs mediate tumour chemotherapy resistance is reviewed, and the potential of exosomal circRNAs in tumour diagnosis, treatment and immune regulation is discussed, providing new ideas for inhibiting tumour chemotherapy resistance.

Keywords: Cancer diagnosis; Chemotherapy resistance; CircRNA; Clinical application; Exosome

DOI: https://doi.org/10.1016/j.biopha.2024.117027

Cell Biochem Biophys. 2024 Jun 22.

Shedding Light on the Role of Exosomal PD-L1 (ExoPD-L1) in Cancer Progression: an Update.

Dongmei Sun, Farag M A Altalbawy, Alexey Yumashev, Ahmed Hjazi, Soumya V Menon, Mandeep Kaur, Mahamedha Deorari, Alzahraa S Abdulwahid, Maha Noori Shakir, Baneen Chasib Gabal.

Exosomes are the primary category of extracellular vesicles (EVs), which are lipid-bilayer vesicles with biological activity spontaneously secreted from either normal or tansformed cells. They serve a crucial role for intercellular communication and affect extracellular environment and the immune system. Tumor-derived exosomes (TEXs) enclose high levels of immunosuppressive proteins, including programmed death-ligand 1 (PD-L1). PD-L1 and its receptor PD-1 act as crucial immune checkpoint molecules, thus facilitating tumor advancement by inhibiting immune responses. PDL-1 is abundantly present on tumor cells and interacts with PD-1 on activated T cells, resulting in T cell suppression and allowing immune evasion of cancer cells. Various FDA-approved monoclonal antibodies inhibiting the PD-1/PD-L1 interaction are commonly used to treat a diverse range of tumors. Although the achieved results are significant, some individuals have a poor reaction to PD-1/PD-L1 blocking. PD-L1-enriched TEXs may mimic the impact of cell-surface PD-L1, consequently potentiating tumor resistance to PD1/PD-L1 based therapy. In light of this, a strong correlation between circulating exosomal PD-L1 levels and response rate to anti-PD-1/PD-L1 antibody treatment has been evinced. This article inspects the function of exosomal PDL-1 in developing resistance to anti-PD-1/PD-L1 therapy for opening new avenues for overcoming tumor resistance to such modalities and development of more favored combination therapy.

Keywords: Cancer; Exosome; Immune cell; PD-1/PD-L1; Progression

DOI: https://doi.org/10.1007/s12013-024-01340-7

FASEB J. 2024 Jul 15. 38(13): e23762

Hypoxia exosome derived CEACAM5 promotes tumor-associated macrophages M2 polarization to accelerate pancreatic neuroendocrine tumors metastasis via MMP9.

Mujie Ye, Feiyu Lu, Danyang Gu, Bingyan Xue, Lin Xu, Chuanhua Hu, Jinhao Chen, Ping Yu, Hongxia Zheng, Yue Gao, Jianhua Wang, Qiyun Tang.

Exosomes play significant roles in the communications between tumor cells and tumor microenvironment. However, the specific mechanisms by which exosomes modulate tumor development under hypoxia in pancreatic neuroendocrine tumors (pNETs) are not well understood. This study aims to investigate these mechanisms and made several important discoveries. We found that hypoxic exosomes derived from pNETs cells can activate tumor-associated macrophages (TAM) to the M2 phenotype, in turn, the M2-polarized TAM, facilitate the migration and invasion of pNETs cells. Further investigation revealed that CEACAM5, a protein highly expressed in hypoxic pNETs cells, is enriched in hypoxic pNETs cell-derived exosomes. Hypoxic exosomal CEACAM5 was observed to induce M2 polarization of TAM through activation of the MAPK signaling pathway. Coculturing pNETs cells with TAM or treated with hypoxic exosomes enhanced the metastatic capacity of pNETs cells. In conclusion, these findings suggest that pNETs cells generate CEACAM5-rich exosomes in a hypoxic microenvironment, which in turn polarize TAM promote malignant invasion of pNETs cells. Targeting exosomal CEACAM5 could potentially serve as a diagnostic and therapeutic strategy for pNETs.

Keywords: CEACAM5; exosome; hypoxia; metastasis; pancreatic neuroendocrine neoplasm

DOI: https://doi.org/10.1096/fj.202302489RRR

Int Immunopharmacol. 2024 Jun 26. pii: S1567-5769(24)00802-6. [Epub ahead of print]138 112282

Exosomal circHIF1A derived from hypoxic-induced carcinoma-associated fibroblasts promotes hepatocellular carcinoma cell malignant phenotypes and immune escape.

Hao Shang, Le Lu, Meng Fan, Yuxuan Lu, Xiali Shi, Hongwei Lu.

Hypoxia is a hallmark of solid tumors. Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment, and CAF-derived exosomes are involved in cancer genesis and progression. Here, this work investigated the role and mechanism of exosomal circHIF1A derived from hypoxia-induced CAFs in hepatocellular carcinoma (HCC) tumorigenesis. CAFs isolated from fresh HCC tissues were incubated in normoxia or hypoxia condition (N/CAFs or H/CAFs), and then the exosomes from N/CAFs or H/CAFs were isolated for functional analysis. Cell proliferation, migration and invasion were analyzed by cell counting kit-8, colony formation, and transwell assays. Immune evasion was evaluated by measuring the cytotoxicity and viability of CD8+T cells. qRT-PCR and western blotting analyses were used for the level measurement of genes and proteins. The binding between Hu antigen R (HuR) and circHIF1A or Programmed death ligand 1 (PD-L1) was analyzed by RNA immunoprecipitation assay. Functionally, we found that CAFs, especially CAFs under hypoxic stress (H/CAFs), promoted the proliferation, migration, invasion and EMT progression in HCC cells, as well as induced immune escape by suppressing CD8+T cell cytotoxicity and activity in an exosome-dependent manner. H/CAFs-derived exosomes showed highly expressed circHIF1A, and could secrete circHIF1A into HCC cells via exosomes. The oncogenic effects of H/CAFs-secreted exosomes were abolished by circHIF1A knockdown. Mechanistically, circHIF1A interacted with HuR to stabilize PD-L1 expression in HCC cells. Meanwhile, circHIF1A silencing suppressed HCC cell proliferation, mobility and immune escape by regulating PD-L1 expression. In all, exosomal circHIF1A derived from hypoxic-induced CAFs promoted the proliferation, migration, invasion, EMT progression and immune escape in HCC cells by up-regulating PD-L1 expression in a HuR-dependent manner.

Keywords: CD8(+)T cells; Exosomes; HCC; HuR; PD-L1; Proliferation

DOI: https://doi.org/10.1016/j.intimp.2024.112282