Extracellular Chaperones as Novel Biomarkers of Overall Cancer Progression and Efficacy of Anticancer Therapy

Exosomal heat shock proteins (Hsps) are involved in intercellular communication both in physiological and pathological conditions. They play a role in key processes of carcinogenesis including immune system regulation, cell differentiation, vascular homeostasis and metastasis formation. Thus, exosomal Hsps are emerging biomarkers of malignancies and possible therapeutic targets. Adolescents and young adults (AYAs) are patients aged 15–39 years. This age group, placed between pediatric and adult oncology, pose a particular challenge for cancer management. New biomarkers of cancer growth and progression as well as prognostic factors are desperately needed in AYAs. In this review, we attempted to summarize the current knowledge on the role of exosomal Hsps in selected solid tumors characteristic for the AYA population and/or associated with poor prognosis in this age group. These included malignant melanoma, brain tumors, and breast, colorectal, thyroid, hepatocellular, lung and gynecological tract carcinomas. The studies on exosomal Hsps in these tumors are limited; however; some have provided promising results. Although further research is needed, there is potential for future clinical applications of exosomal Hsps in AYA cancers, both as novel biomarkers of disease presence, progression or relapse, or as therapeutic targets or tools for drug delivery.

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Role of Regulatory Oncogenic or Tumor Suppressor miRNAs of PI3K/AKT Signaling Axis in the Pathogenesis of Colorectal Cancer

Current Pharmaceutical Design ◽

10.2174/1381612825666190110151957 ◽

2019 ◽

Vol 24 (39) ◽

pp. 4605-4610 ◽

Cited By ~ 7

Author(s):

Atena Soleimani ◽

Farzad Rahmani ◽

Gordon A. Ferns ◽

Mikhail Ryzhikov ◽

Amir Avan ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Suppressor ◽

Current Knowledge ◽

Akt Signaling ◽

Tumor Tissues ◽

Radio Therapy ◽

Signaling Axis ◽

Cancer Tumor ◽

Novel Biomarkers

Colorectal cancer (CRC) is the leading cause of cancer death worldwide and its incidence is increasing. In most patients with CRC, the PI3K/AKT signaling axis is over-activated. Regulatory oncogenic or tumor suppressor microRNAs (miRNAs) for PI3K/AKT signaling regulate cell proliferation, migration, invasion, angiogenesis, as well as resistance to chemo-/radio-therapy in colorectal cancer tumor tissues. Thus, regulatory miRNAs of PI3K/AKT/mTOR signaling represent novel biomarkers for new patient diagnosis and obtaining clinically invaluable information from post-treatment CRC patients for improving therapeutic strategies. This review summarizes the current knowledge of miRNAs’ regulatory roles of PI3K/AKT signaling in CRC pathogenesis.

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miRNA-mRNA integrative analysis in primary myelofibrosis CD34+ cells: role of miR-155/JARID2 axis in abnormal megakaryopoiesis

Blood ◽

10.1182/blood-2013-12-544197 ◽

2014 ◽

Vol 124 (13) ◽

pp. e21-e32 ◽

Cited By ~ 74

Author(s):

Ruggiero Norfo ◽

Roberta Zini ◽

Valentina Pennucci ◽

Elisa Bianchi ◽

Simona Salati ◽

...

Keyword(s):

Expression Analysis ◽

Mirna Expression ◽

Therapeutic Targets ◽

Primary Myelofibrosis ◽

Integrative Analysis ◽

Cd34 Cells ◽

Key Points ◽

Differential Gene ◽

New Biomarkers

Key Points Differential gene and miRNA expression analysis in PMF granulocytes identifies new biomarkers and putative therapeutic targets. Activation of the miR-155/JARID2 axis in PMF CD34+ cells results in overproduction of MK precursors.

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Role of microRNAs in Venous Thromboembolism

International Journal of Molecular Sciences ◽

10.3390/ijms21072602 ◽

2020 ◽

Vol 21 (7) ◽

pp. 2602 ◽

Cited By ~ 1

Author(s):

Vânia M. Morelli ◽

Sigrid K. Brækkan ◽

John-Bjarne Hansen

Keyword(s):

Venous Thromboembolism ◽

Animal Models ◽

Statistical Power ◽

Current Knowledge ◽

Thrombus Formation ◽

Therapeutic Targets ◽

Small Sample ◽

Future Research ◽

Gene Expressions

MicroRNAs (miRNAs) are non-coding RNAs that execute their function by targeted downregulation of gene expressions. There is growing evidence from epidemiological studies and animal models suggesting that the expression level of miRNAs is dysregulated in venous thromboembolism (VTE). In this review, we summarize the current knowledge on the role of miRNAs as biomarkers for VTE and provide general insight into research exploring the modulation of miRNA activity in animal models of venous thrombosis. Up to now, published studies have yielded inconsistent results on the role of miRNAs as biomarkers for VTE with most of the reports focused on diagnostic research. The limited statistical power of the individual studies, due to the small sample sizes, may substantially contribute to the poor reproducibility among studies. In animal models, over-expression or inhibition of some miRNAs appear to influence venous thrombus formation and resolution. However, there is an important gap in knowledge on the potential role of miRNAs as therapeutic targets in VTE. Future research involving large cohorts should be designed to clarify the clinical usefulness of miRNAs as biomarkers for VTE, and animal model studies should be pursued to unravel the role of miRNAs in the pathogenesis of VTE and their potential as therapeutic targets.

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Chemokines—What Is Their Role in Colorectal Cancer?

Cancer Control ◽

10.1177/1073274820903384 ◽

2020 ◽

Vol 27 (1) ◽

pp. 107327482090338 ◽

Cited By ~ 2

Author(s):

Sara Pączek ◽

Marta Łukaszewicz-Zając ◽

Barbara Mroczko

Keyword(s):

Colorectal Cancer ◽

Current Knowledge ◽

Early Stage ◽

Distant Metastases ◽

Cell Types ◽

Diagnosis And Prognosis ◽

Novel Biomarkers ◽

Specific Receptors ◽

Common Malignancy

Colorectal cancer (CRC) is one of the leading causes of cancer-related death. It is the second most frequently diagnosed malignancy in Europe and third worldwide. Colorectal malignancies diagnosed at an early stage offer a promising survival rate. However, advanced tumors often present distant metastases even after the complete resection of a primary tumor. Therefore, novel biomarkers of CRC are sorely needed in the diagnosis and prognosis of this common malignancy. A family of chemokines are composed of small, secreted proteins. They are best known for their ability to stimulate the migration of several cell types. Some investigations have indicated that chemokines are involved in cancer development, including CRC. This article presents current knowledge regarding chemokines and their specific receptors in CRC progression. Moreover, the prime aim of this review is to summarize the potential role of these proteins as biomarkers in the diagnosis and prognosis of CRC.

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Dissimilar Appearances Are Deceptive–Common microRNAs and Therapeutic Strategies in Liver Cancer and Melanoma

Cells ◽

10.3390/cells9010114 ◽

2020 ◽

Vol 9 (1) ◽

pp. 114

Author(s):

Lisa Linck-Paulus ◽

Claus Hellerbrand ◽

Anja K. Bosserhoff ◽

Peter Dietrich

Keyword(s):

Cancer Progression ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Therapeutic Targets ◽

Genetic Alterations ◽

Therapeutic Strategies ◽

The Future ◽

Associated Proteins ◽

Cancer Types ◽

Novel Therapeutic Strategies

In this review, we summarize the current knowledge on miRNAs as therapeutic targets in two cancer types that were frequently described to be driven by miRNAs—melanoma and hepatocellular carcinoma (HCC). By focusing on common microRNAs and associated pathways in these—at first sight—dissimilar cancer types, we aim at revealing similar molecular mechanisms that are evolved in microRNA-biology to drive cancer progression. Thereby, we also want to outlay potential novel therapeutic strategies. After providing a brief introduction to general miRNA biology and basic information about HCC and melanoma, this review depicts prominent examples of potent oncomiRs and tumor-suppressor miRNAs, which have been proven to drive diverse cancer types including melanoma and HCC. To develop and apply miRNA-based therapeutics for cancer treatment in the future, it is essential to understand how miRNA dysregulation evolves during malignant transformation. Therefore, we highlight important aspects such as genetic alterations, miRNA editing and transcriptional regulation based on concrete examples. Furthermore, we expand our illustration by focusing on miRNA-associated proteins as well as other regulators of miRNAs which could also provide therapeutic targets. Finally, design and delivery strategies of miRNA-associated therapeutic agents as well as potential drawbacks are discussed to address the question of how miRNAs might contribute to cancer therapy in the future.

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The Impact of miRNA in Colorectal Cancer Progression and Its Liver Metastases

International Journal of Molecular Sciences ◽

10.3390/ijms19123711 ◽

2018 ◽

Vol 19 (12) ◽

pp. 3711 ◽

Cited By ~ 22

Author(s):

Ovidiu Balacescu ◽

Daniel Sur ◽

Calin Cainap ◽

Simona Visan ◽

Daniel Cruceriu ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastasis ◽

Liver Metastases ◽

Cancer Progression ◽

Dependent Manner ◽

Mesenchymal Transition ◽

Cancer Management ◽

Incidence And Mortality ◽

The Impact

Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies with a high incidence and mortality rate. An essential challenge in colorectal cancer management is to identify new prognostic factors that could better estimate the evolution and treatment responses of this disease. Considering their role in cancer development, progression and metastasis, miRNAs have become an important class of molecules suitable for cancer biomarkers discovery. We performed a systematic search of studies investigating the role of miRNAs in colorectal progression and liver metastasis published until October 2018. In this review, we present up-to-date information regarding the specific microRNAs involved in CRC development, considering their roles in alteration of Wnt/βcatenin, EGFR, TGFβ and TP53 signaling pathways. We also emphasize the role of miRNAs in controlling the epithelial–mesenchymal transition of CRC cells, a process responsible for liver metastasis in a circulating tumor cell-dependent manner. Furthermore, we discuss the role of miRNAs transported by CRC-derived exosomes in mediating liver metastases, by preparing the secondary pre-metastatic niche and in inducing liver carcinogenesis in a Dicer-dependent manner.

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Emerging Role of Podocalyxin in the Progression of Mature B-Cell Non-Hodgkin Lymphoma

Cancers ◽

10.3390/cancers12020396 ◽

2020 ◽

Vol 12 (2) ◽

pp. 396

Author(s):

Estíbaliz Tamayo-Orbegozo ◽

Laura Amo ◽

Javier Díez-García ◽

Elena Amutio ◽

Marta Riñón ◽

...

Keyword(s):

Drug Resistance ◽

B Cell ◽

Hodgkin Lymphoma ◽

Cancer Progression ◽

Current Knowledge ◽

Cell Types ◽

Metabolic Reprogramming ◽

Non Hodgkin Lymphoma ◽

New Evidence

Mature B-cell non-Hodgkin lymphoma (B-NHL) constitutes a group of heterogeneous malignant lymphoproliferative diseases ranging from indolent to highly aggressive forms. Although the survival after chemo-immunotherapy treatment of mature B-NHL has increased over the last years, many patients relapse or remain refractory due to drug resistance, presenting an unfavorable prognosis. Hence, there is an urgent need to identify new prognostic markers and therapeutic targets. Podocalyxin (PODXL), a sialomucin overexpressed in a variety of tumor cell types and associated with their aggressiveness, has been implicated in multiple aspects of cancer progression, although its participation in hematological malignancies remains unexplored. New evidence points to a role for PODXL in mature B-NHL cell proliferation, survival, migration, drug resistance, and metabolic reprogramming, as well as enhanced levels of PODXL in mature B-NHL. Here, we review the current knowledge on the contribution of PODXL to tumorigenesis, highlighting and discussing its role in mature B-NHL progression.

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miRNAs as novel biomarkers in the management of prostate cancer

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2015-1073 ◽

2017 ◽

Vol 55 (5) ◽

Cited By ~ 42

Author(s):

Xavier Filella ◽

Laura Foj

Keyword(s):

Prostate Cancer ◽

Current Knowledge ◽

Expression Patterns ◽

Specific Antigen ◽

Digital Rectal Examination ◽

New Approach ◽

Novel Biomarkers ◽

Non Coding Rnas ◽

Underlying Mechanisms ◽

New Biomarkers

AbstractmicroRNAs (miRNAs) are small non-coding RNAs that control gene expression posttranscriptionally and are part of the giant non codifying genoma. Cumulating data suggest that miRNAs are promising potential biomarkers for many diseases, including cancer. Prostate cancer (PCa) detection is currently based in the serum prostate-specific antigen biomarker and digital rectal examination. However, these methods are limited by a low predictive value and the adverse consequences associated with overdiagnosis and overtreatment. New biomarkers that could be used for PCa detection and prognosis are still needed. Recent studies have demonstrated that aberrant expressions of microRNAs are associated with the underlying mechanisms of PCa. This review attempts to extensively summarize the current knowledge of miRNA expression patterns, as well as their targets and involvement in PCa pathogenesis. We focused our review in the value of circulating and urine miRNAs as biomarkers in PCa patients, highlighting the existing discrepancies between different studies, probably associated with the important methodological issues related to their quantitation and normalization. The majority of studies have been performed in serum or plasma, but urine obtained after prostate massage appears as a new way to explore the usefulness of miRNAs. Large screening studies to select a miRNA profile have been completed, but bioinformatics tools appear as a new approach to select miRNAs that are relevant in PCa development. Promising preliminary results were published concerning miR-141, miR-375 and miR-21, but larger and prospective studies using standardized methodology are necessary to define the value of miRNAs in the detection and prognosis of PCa.

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The Role of miR-107 in Prostate Cancer: A Review and Experimental Evidence

10.5772/intechopen.98281 ◽

2021 ◽

Author(s):

Maria Elizbeth Alvarez-Sanchez ◽

Oscar Rojas Espinosa ◽

Julio César Torres-Romero ◽

Ereth Ameyatzin Robles Chávez ◽

Edgar Estrella-Parra ◽

...

Keyword(s):

Prostate Cancer ◽

Experimental Evidence ◽

Cancer Progression ◽

Signaling Cascades ◽

Potential Utility ◽

Diagnosis And Prognosis ◽

Endogenous Regulators ◽

New Biomarkers

Over the past two decades, several research groups have focused on the functioning of microRNAs (miRNAs), because many of them function as positive or negative endogenous regulators of processes that alter during the development of cancer. Prostate cancer is the second most commonly occurring cancer in men. New biomarkers are needed to support the diagnosis of prostate cancer. Although it is necessary to deepen the research on this molecule to explore its potential utility in the diagnosis, follow-up, and prognosis of cancer, our results support a role of miR-107 in the signaling cascades that allow cancer progression, and as shown here, in the progression of Prostate Cancer (PCa). These findings strongly suggest that miR-107 may be a potential circulating biomarker for the diagnosis and prognosis of prostate cancer.

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Heat Shock Proteins in Oxidative Stress and Ischemia/Reperfusion Injury and Benefits from Physical Exercises: A Review to the Current Knowledge

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/6678457 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Jakub Szyller ◽

Iwona Bil-Lula

Keyword(s):

Oxidative Stress ◽

Heat Shock ◽

Heat Shock Proteins ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Current Knowledge ◽

Ischemia Reperfusion ◽

Physical Exercises ◽

Shock Proteins

Heat shock proteins (HSPs) are molecular chaperones produced in response to oxidative stress (OS). These proteins are involved in the folding of newly synthesized proteins and refolding of damaged or misfolded proteins. Recent studies have been focused on the regulatory role of HSPs in OS and ischemia/reperfusion injury (I/R) where reactive oxygen species (ROS) play a major role. ROS perform many functions, including cell signaling. Unfortunately, they are also the cause of pathological processes leading to various diseases. Biological pathways such as p38 MAPK, HSP70 and Akt/GSK-3β/eNOS, HSP70, JAK2/STAT3 or PI3K/Akt/HSP70, and HSF1/Nrf2-Keap1 are considered in the relationship between HSP and OS. New pathophysiological mechanisms involving ROS are being discovered and described the protein network of HSP interactions. Understanding of the mechanisms involved, e.g., in I/R, is important to the development of treatment methods. HSPs are multifunctional proteins because they closely interact with the antioxidant and the nitric oxide generation systems, such as HSP70/HSP90/NOS. A deficiency or excess of antioxidants modulates the activation of HSF and subsequent HSP biosynthesis. It is well known that HSPs are involved in the regulation of several redox processes and play an important role in protein-protein interactions. The latest research focuses on determining the role of HSPs in OS, their antioxidant activity, and the possibility of using HSPs in the treatment of I/R consequences. Physical exercises are important in patients with cardiovascular diseases, as they affect the expression of HSPs and the development of OS.

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