bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2022–10–09
eight papers selected by
Muhammad Rizwan, COMSATS University
  1. Exosomal circPRRX1 functions as a ceRNA for miR-596 to promote the proliferation, migration, invasion, and reduce radiation sensitivity of gastric cancer cells via the upregulation of NF-κB activating protein.
  2. OncomiRs as noncoding RNAs having functions in cancer: Their role in immune suppression and clinical implications.
  3. Urine exosomes as biomarkers in bladder cancer diagnosis and prognosis: From functional roles to clinical significance.
  4. Exosome-mediated transfer of circ_0063526 enhances cisplatin resistance in gastric cancer cells via regulating miR-449a/SHMT2 axis.
  5. Exosomes as Delivery Systems for Targeted Tumour Therapy: A Systematic Review and Meta-analysis of In vitro Studies.
  6. The Exosomal miR-1246 of Laryngeal Squamous Cell Carcinoma Induces Polarization of M2 Type Macrophages and Promotes the Invasiveness of Laryngeal Squamous Cell Carcinoma.
  7. Melanoma stem cells promote metastasis via exosomal miR-1268a inactivation of autophagy.
  8. Characterization of blood-derived exosomal hTERT mRNA as a biomarker for colon cancer and Lynch syndrome.
  1. Anticancer Drugs. 2022 Oct 06.
    Exosomal circPRRX1 functions as a ceRNA for miR-596 to promote the proliferation, migration, invasion, and reduce radiation sensitivity of gastric cancer cells via the upregulation of NF-κB activating protein.
    Yuxin He, Liangjian Zheng, Mengzhen Yuan, Jia Fan, Liwen Rong, Tingting Zhan, Jun Zhang.
      Exosomes, which are small extracellular vesicles, have been unveiled to carry circular RNAs (circRNAs). CircRNA paired-related homeobox 1 (circPRRX1) can be transferred by exosomes derived from gastric cancer cells. Here, we investigated the activity and mechanism of exosomal circPRRX1 in gastric tumorigenesis and radiation sensitivity. CircPRRX1, microRNA (miR)-596, and NF-κB activating protein (NKAP) were quantified by quantitative real-time PCR and immunoblotting. Cell proliferation, motility, and invasion were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and transwell assays, respectively. Cell colony formation and survival were assessed by colony formation assays. Dual-luciferase reporter assays were performed to verify the direct relationship between miR-596 and circPRRX1 or NKAP. In-vivo xenograft studies were used to evaluate the role of exosomal circPRRX1 in tumor growth. Our data showed that circPRRX1 expression was elevated in human gastric cancer, and circPRRX1 could be transferred by exosomes from gastric cancer cells. Exosomal circPRRX1 affected cell proliferation, motility, invasion, and radiation sensitivity in vitro and tumor growth in vivo. Mechanistically, circPRRX1 directly regulated miR-596 expression, and exosomal circPRRX1 affected cell biological functions at least in part through miR-596. NKAP was identified as a direct target and functionally downstream effector of miR-596. Exosomal circPRRX1 modulated NKAP expression by acting as a competing endogenous RNA (ceRNA) for miR-596. Our findings suggest a new mechanism, the exosomal circPRRX1/miR-596/NKAP ceRNA crosstalk, in regulating gastric tumorigenesis and radiation sensitivity.
    DOI:  https://doi.org/10.1097/CAD.0000000000001358
  2. Front Immunol. 2022 ;13 913951
    OncomiRs as noncoding RNAs having functions in cancer: Their role in immune suppression and clinical implications.
    Khalid Otmani, Redouane Rouas, Philippe Lewalle.
      Currently, microRNAs have been established as central players in tumorigenesis, but above all, they have opened an important door for our understanding of immune and tumor cell communication. This dialog is largely due to onco-miR transfer from tumor cells to cells of the tumor microenvironment by exosome. This review outlines recent advances regarding the role of oncomiRs in enhancing cancer and how they modulate the cancer-related immune response in the tumor immune microenvironment. MicroRNAs (miRNAs) are a type of noncoding RNA that are important posttranscriptional regulators of messenger RNA (mRNA) translation into proteins. By regulating gene expression, miRNAs enhance or inhibit cancer development and participate in several cancer biological processes, including proliferation, invasion metastasis, angiogenesis, chemoresistance and immune escape. Consistent with their widespread effects, miRNAs have been categorized as oncogenes (oncomiRs) or tumor suppressor (TS) miRNAs. MiRNAs that promote tumor growth, called oncomiRs, inhibit messenger RNAs of TS genes and are therefore overexpressed in cancer. In contrast, TS miRNAs inhibit oncogene messenger RNAs and are therefore underexpressed in cancer. Endogenous miRNAs regulate different cellular pathways in all cell types. Therefore, they are not only key modulators in cancer cells but also in the cells constituting their microenvironments. Recently, it was shown that miRNAs are also involved in intercellular communication. Indeed, miRNAs can be transferred from one cell type to another where they regulate targeted gene expression. The primary carriers for the transfer of miRNAs from one cell to another are exosomes. Exosomes are currently considered the primary carriers for communication between the tumor and its surrounding stromal cells to support cancer progression and drive immune suppression. Exosome and miRNAs are seen by many as a hope for developing a new class of targeted therapy. This review outlines recent advances in understanding the role of oncomiRs in enhancing cancer and how they promote its aggressive characteristics and deeply discusses the role of oncomiRs in suppressing the anticancer immune response in its microenvironment. Additionally, further understanding the mechanism of oncomiR-related immune suppression will facilitate the use of miRNAs as biomarkers for impaired antitumor immune function, making them ideal immunotherapy targets.
    Keywords:  cancer immune modulation; extracellular vesicles; miRNAs; oncomiRs; tumor immune microenvironment
    DOI:  https://doi.org/10.3389/fimmu.2022.913951
  3. Front Oncol. 2022 ;12 1019391
    Urine exosomes as biomarkers in bladder cancer diagnosis and prognosis: From functional roles to clinical significance.
    Nicholas Lee, Ashan Canagasingham, Mohit Bajaj, Ramesh Shanmugasundaram, Anthony Hutton, Joseph Bucci, Peter Graham, James Thompson, Jie Ni.
      Bladder cancer is one of the top ten most common cancers and top ten causes of cancer death globally. 5-year survival rates have decreased in Australia from 66% to 55% in the past three decades. The current gold standard for diagnosis is cystoscopy. However, cystoscopies are an invasive and health-resource intensive procedure which has sub-optimal sensitivity for flat lesions such as CIS (carcinoma in situ) and low specificity for differentiating inflammation from cancer - hence requiring biopsies under anesthesia. Frequent and life-long surveillance cystoscopy is required for most patients since there are high rates of progression and local recurrence in high-risk non-muscle invasive cancer (NMIBC) as well as poor outcomes associated with delayed detection of muscle-invasive bladder cancer (MIBC). There is an unmet need for a non-invasive test to provide better discrimination and risk-stratification of bladder cancer which could aid clinicians by improving patient selection for cystoscopy; enhanced risk stratification methods may guide the frequency of surveillance cystoscopies and inform treatment choices. Exosomes, which are nano-sized extracellular vesicles containing genetic material and proteins, have been shown to have functional roles in the development and progression of bladder cancer. Exosomes have also been demonstrated to be a robust source of potential biomarkers for bladder cancer diagnosis and prognosis and may also have roles as therapeutic agents. In this review, we summarize the latest evidence of biological roles of exosomes in bladder cancer and highlight their clinical significance in bladder cancer diagnosis, surveillance and treatment.
    Keywords:  biomarker; bladder cancer; diagnosis; exosome; liquid biopsy
    DOI:  https://doi.org/10.3389/fonc.2022.1019391
  4. Anticancer Drugs. 2022 Sep 30.
    Exosome-mediated transfer of circ_0063526 enhances cisplatin resistance in gastric cancer cells via regulating miR-449a/SHMT2 axis.
    Gang Yang, Jie Tan, Jian Guo, Zhiwei Wu, Qiong Zhan.
      Exosomes are critical mediators of intercellular communication. Exosomal circular RNAs (circRNAs) have been reported to play critical roles in the development of chemoresistance in various tumors, including gastric cancer. However, the role of exosomal circ_0063526 in cisplatin (CDDP) resistance of gastric cancer is still unclear. The expression of circ_0063526, microRNA-449a (miR-449a) and serine hydroxymethyltransferase 2 (SHMT2) mRNA was determined by quantitative real-time PCR (qRT-PCR). Cell viability was assessed by the Cell Counting Kit-8 assay. Cell migration and invasion were evaluated by the transwell assay and wound healing assay. Western blot assay was used to measure the protein expression of light Chain 3 (LC3) I/II, p62 and SHMT2. Exosomes were detected using transmission electron microscopy. The size distribution of exosomes was analyzed by nanoparticle tracking analysis. The interaction between miR-449a and circ_0063526 or SHMT2 was confirmed by a dual-luciferase reporter and RNA pull-down assays. Circ_0063526 expression was increased in gastric cancer tissues and cells and CDDP-resistant cells. Extracellular circ_0063526 could be packaged into exosomes and transmitted to sensitive cells, thus disseminating CDDP resistance. Knockdown of exosomal circ_0063526 inhibited CDDP resistance via suppressing migration, invasion and autophagy in gastric cancer cells. Moreover, circ_0063526 was identified as a molecular sponge of miR-449a to upregulate SHMT2 expression. Further, exosomal circ_0063526 regulated SHMT2 expression to enhance CDDP resistance of gastric cancer cells. Additionally, high expression of exosomal circ_0063526 in serum was associated with poor response to CDDP treatment in gastric cancer patients. Exosomal circ_0063526 facilitated CDDP resistance in gastric cancer via regulating the miR-449a/SHMT2 axis.
    DOI:  https://doi.org/10.1097/CAD.0000000000001386
  5. Pharm Nanotechnol. 2022 Sep 30.
    Exosomes as Delivery Systems for Targeted Tumour Therapy: A Systematic Review and Meta-analysis of In vitro Studies.
    Suleiman Alhaji Muhammad, Jaafaru Sani Mohammed, Sulaiman Rabiu.
       BACKGROUND: Delivery systems with low immunogenicity and toxicity are believed to enhance the efficacy of specific targeted drug delivery to cancer cells. Exosomes are potential natural nanosystems that can enhance the delivery of therapeutic agents for targeted cancer therapy.
    OBJECTIVE: This study provides a precise effect size of exosomes as nanovesicles for in vitro delivery of anticancer agents.
    METHOD: In this systematic review and meta-analysis, the efficacy of exosomes as nanocarriers for the delivery of therapeutic molecules was investigated using the random-effects model. We did comprehensive literature searches through CINAHL, Cochrane, PubMed, Scopus, and Science Direct of in vitro studies that reported exosomes as delivery systems for cancer therapy.
    RESULTS: After the screening of eligible articles, a total of 50 studies were enrolled for the meta-analysis. The results showed that cancer cells treated with exosome-loaded anticancer agents for at least 6 h significantly decreased cell viability and increased cytotoxicity with the standardized mean difference [SMD] of -1.47 [-2.18, -0.76; [p<0.0001] and -1.66 [-2.71, -0.61; p<0.002]. Exosomes effectively delivered drugs and exogenous miRNAs, siRNAs, viruses, and enzymes to cancer cells in vitro.
    CONCLUSION: This meta-analysis provides evidence of exosomes as efficient nanocarriers for the delivery of anticancer drugs.
    Keywords:  Cancer cells; Cytotoxicity; Drug delivery vehicles; Exosomes; In vitro studies
    DOI:  https://doi.org/10.2174/2211738510666220930155253
  6. J Oncol. 2022 ;2022 4424221
    The Exosomal miR-1246 of Laryngeal Squamous Cell Carcinoma Induces Polarization of M2 Type Macrophages and Promotes the Invasiveness of Laryngeal Squamous Cell Carcinoma.
    Lifeng Wu, Na Zuo, Shuo Pan, Yue Wang, Qixue Wang, Jun Ma.
       Background: The possible role and detailed mechanisms of Tumor-associated macrophages (TAMs) in laryngeal squamous cell carcinoma (LSCC) have not been revealed.
    Methods: The expressions of typical markers were evaluated by qRT-PCR. In macrophages cocultured with TU212 cells, CD163, and CD206 protein expressions were detected by western blot analysis; IL-10 and IL-12 expressions were detected by ELISA assay. Exosomes isolated from TU212 cells were characterized by TEM analysis. As for the TU212 cells cocultured with macrophages processed with HOK or TU212 cells derived exosomes, their viability, migration, and invasion were assessed by CCK-8 assay, wounding healing, and Transwell assays, respectively.
    Results: In this study, macrophages processed with exosomes from human TU212 cells notably advanced LSCC cell viability, migration, and invasion. miR-1246 inhibitor suppressed the M2 polarization of macrophages. Macrophages transfected with miR-1246 inhibitor suppressed LSCC cell viability, migration, and invasion.
    Conclusion: In summary, our data implied that the exosomal, miR-1246 of LSCC, induced polarization of M2 type macrophages and promoted the progression of LSCC. This trial is registered with 2020-13.
    DOI:  https://doi.org/10.1155/2022/4424221
  7. Biol Res. 2022 Oct 01. 55(1): 29
    Melanoma stem cells promote metastasis via exosomal miR-1268a inactivation of autophagy.
    Xiaoshuang Li, Doudou Liu, Hao Chen, Bin Zeng, Qiting Zhao, Yuhan Zhang, Yuting Chen, Jianyu Wang, H Rosie Xing.
       BACKGROUND: Metastatic melanoma has a high mortality rate and poor survival. This is associated with efficient metastatic colonization, but the underlying mechanisms remain elusive. Communication between cancer stem cells (CSCs) and cancer cells plays an important role in metastatic dissemination. Whether cancer stem cells can alter the metastatic properties of non-CSC cells; and whether exosomal crosstalk can mediate such interaction, have not been demonstrated in melanoma prior to this report.
    RESULTS: The results revealed that exosomes secreted by highly metastatic melanoma CSCs (OL-SCs) promoted the invasiveness of the low metastatic melanoma cells (OL) and accelerated metastatic progression. miR-1268a was up-regulated in cells and exosomes of OL-SCs. Moreover, OL-SCs-derived exosomal miR-1268a, upon taking up by OL cells, promoted the metastatic colonization ability of OL cells in vitro and in vivo. In addition, the pro-metastatic activity of exosomal miR-1268a is achieved through inhibition of autophagy.
    CONCLUSION: Our study demonstrates that OL cells can acquire the "metastatic ability" from OL-SCs cells. OL-SCs cells achieves this goal by utilizing its exosomes to deliver functional miRNAs, such as miR-1268a, to the targeted OL cells which in turn augments metastatic colonization by inactivating the autophagy pathway in OL cells.
    Keywords:  Autophagy; Exosomes; Melanoma stem cells; Metastasis; miR-1268a
    DOI:  https://doi.org/10.1186/s40659-022-00397-z
  8. Front Oncol. 2022 ;12 962473
    Characterization of blood-derived exosomal hTERT mRNA as a biomarker for colon cancer and Lynch syndrome.
    Ido Laish, Zohar Levi, Hussein Mahajna, Ahmad Albshesh, Nir Horesh, Efraim Katz, Dan Feldman, Nadav Shinar, Orit Picard, Miri Yavzori, Ella Fudim, Pia Raanani, Tamar Berger, Hadar Goldvaser, Einat Beery, Orit Uziel.
       Background: Human telomerase reverse transcriptase (hTERT)- mRNA was shown to be elevated in exosomes derived from the sera of a variety of hematological and solid cancer patients. We aimed to evaluate its role as a diagnostic marker in patients with newly diagnosed colon cancer and in hereditary syndromes with predisposition to colon cancer.
    Methods: hTERT -mRNA levels were determined in serum-derived exosomes from 88 patients with colon cancer, 71 Lynch-syndrome carriers with unknown active malignancies and 50 healthy controls. Data, including demographics, background diseases, clinical data regarding tumor characteristics and genetic data, were retrieved data from medical files.
    Results: Patients with colon cancer had both higher exosomal hTERT mRNA levels and a higher proportion of patients with positive exosomal hTERT mRNA than controls (29.5% vs. 4%, respectively, P values < 0.001). Within the cancer group, patients with a metastatic disease had higher levels of telomerase mRNA than non-metastatic disease patients, and these levels correlated with CEA levels. Likewise, Lynch syndrome carriers had a higher proportion of positive exosomal hTERT mRNA than controls (21.1% vs. 4%, respectively, P value 0.008) but only a trend towards higher exosomal hTERT mRNA levels. Higher telomerase mRNA levels were not correlated with the mutated gene.
    Conclusions: Exosomal serum hTERT -mRNA levels are associated with metastatic colon cancer and were also demonstrated in a subset of Lynch syndrome carriers. Its significance as a biomarker for developing malignancy should be elucidated.
    Keywords:  Lynch syndrome; colon cancer; exosomes; genetic syndromes; telomerases
    DOI:  https://doi.org/10.3389/fonc.2022.962473
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