RESUMEN

In the intricate field of cancer biology, researchers are increasingly intrigued by the emerging role of exosomal long non-coding RNAs (lncRNAs) due to their multifaceted interactions, complex modulation mechanisms, and potential therapeutic applications. These exosomal lncRNAs, carried within extracellular vesicles, play a vital partin tumorigenesis and disease progression by facilitating communication networks between tumor cells and their local microenvironment, making them an ideal candidates for use in a liquid biopsy approach. However, exosomal lncRNAs remain an understudied area, especially in cancer biology. Therefore this review aims to comprehensively explore the dynamic interplay between exosomal lncRNAs and various cellular components, including interactions with tumor-stroma, immune modulation, and drug resistance mechanisms. Understanding the regulatory functions of exosomal lncRNAs in these processes can potentially unveil novel diagnostic markers and therapeutic targets for cancer. Additionally, the emergence of RNA-based therapeutics presents exciting opportunities for targeting exosomal lncRNAs, offering innovative strategies to combat cancer progression and improve treatment outcomes. Thus, this review provides insights into the current understanding of exosomal lncRNAs in cancer biology, highlighting their crucial roles, regulatory mechanisms, and the evolving landscape of therapeutic interventions. Furthermore, we have also discussed the advantage of exosomes as therapeutic carriers of lncRNAs for the development of personalized targeted therapy for cancer patients.

RESUMEN

Prostate cancer (PCa) continues to be the most diagnosed cancer and the second primary cause of fatalities in men globally. There is an abundance of scientific evidence suggesting that the human microbiome, together with its metabolites, plays a crucial role in carcinogenesis and has a significant impact on the efficacy of anticancer interventions in solid and hematological cancers. These anticancer interventions include chemotherapy, immune checkpoint inhibitors, and targeted therapies. Furthermore, the microbiome can influence systemic and local immune responses using numerous metabolites such as short-chain fatty acids (SCFAs). Despite the lack of scientific data in terms of the role of SCFAs in PCa pathogenesis, recent studies show that SCFAs have a profound impact on PCa progression. Several studies have reported racial/ethnic disparities in terms of bacterial content in the gut microbiome and SCFA composition. These studies explored microbiome and SCFA racial/ethnic disparities in cancers such as colorectal, colon, cervical, breast, and endometrial cancer. Notably, there are currently no published studies exploring microbiome/SCFA composition racial disparities and their role in PCa carcinogenesis. This review discusses the potential role of the microbiome in PCa development and progression. The involvement of microbiome-derived SCFAs in facilitating PCa carcinogenesis and their effect on PCa therapeutic response, particularly immunotherapy, are discussed. Racial/ethnic differences in microbiome composition and SCFA content in various cancers are also discussed. Lastly, the effects of SCFAs on PCa progression via epigenetic modifications is also discussed.

RESUMEN

Colorectal cancer (CRC) ranks as one of the top causes of cancer mortality worldwide and its incidence is on the rise, particularly in low-middle-income countries (LMICs). There are several factors that contribute to the development and progression of CRC. Alternative splicing (AS) was found to be one of the molecular mechanisms underlying the development and progression of CRC. With the advent of genome/transcriptome sequencing and large patient databases, the broad role of aberrant AS in cancer development and progression has become clear. AS affects cancer initiation, proliferation, invasion, and migration. These splicing changes activate oncogenes or deactivate tumor suppressor genes by producing altered amounts of normally functional or new proteins with different, even opposing, functions. Thus, identifying and characterizing CRC-specific alternative splicing events and variants might help in designing new therapeutic splicing disrupter drugs. CRC-specific splicing events can be used as diagnostic and prognostic biomarkers. In this review, alternatively spliced events and their role in CRC development will be discussed. The paper also reviews recent research on alternatively spliced events that might be exploited as prognostic, diagnostic, and targeted therapeutic indicators. Of particular interest is the targeting of protein arginine methyltransferase (PMRT) isoforms for the development of new treatments and diagnostic tools. The potential challenges and limitations in translating these discoveries into clinical practice will also be addressed.

RESUMEN

Cancer is a global health concern with rising incidence, morbidity, and mortality. The interaction between the tumor and immune cells within the tumor microenvironment is facilitated by signaling pathways driven by immunomodulatory proteins. Alternative splicing regulates the production of multiple immunomodulatory proteins with diverse functionality from a single mRNA transcript. Splicing factors are pivotal in modulating alternative splicing processes but are also subject to regulation. The dysregulation of alternative splicing may result from splicing factor (SF) abnormal expression levels and mutations in the cis and trans-acting elements and small nuclear RNA (snRNA) molecules. Aberrant splicing may generate abnormal mRNA transcripts encoding isoforms with altered functions that contribute to tumorigenesis or cancer progression. This review uncovers the complexity of immunomodulatory genes splicing dysregulation in oncogenesis. Identifying specific immunomodulatory splicing isoforms that contribute to cancer could be utilized to improve current immunotherapeutic drugs or develop novel therapeutic interventions for cancer.

Asunto(s)

Carcinogénesis , Transformación Celular Neoplásica , Humanos , Carcinogénesis/genética , Transformación Celular Neoplásica/genética , Ingeniería Genética , Empalme Alternativo/genética , ARN Mensajero , Microambiente Tumoral/genética

RESUMEN

Angiogenesis, the generation of new blood vessels, is one of the hallmarks of cancer. The growing tumor requires nutrients and oxygen. Recent evidence has shown that tumors release signals to attract new nerve fibers and stimulate the growth of new nerve fibers. Neurogenesis, neural extension, and axonogenesis assist in the migration of cancer cells. Cancer cells can use both blood vessels and nerve fibers as routes for cells to move along. In this way, neurogenesis and angiogenesis both contribute to cancer metastasis. As a result, tumor-induced neurogenesis joins angiogenesis and immunosuppression as aberrant processes that are exacerbated within the tumor microenvironment. The relationship between these processes contributes to cancer development and progression. The interplay between these systems is brought about by cytokines, neurotransmitters, and neuromodulators, which activate signaling pathways that are common to angiogenesis and the nervous tissue. These include the AKT signaling pathways, the MAPK pathway, and the Ras signaling pathway. These processes also both require the remodeling of tissues. The interplay of these processes in cancer provides the opportunity to develop novel therapies that can be used to target these processes.

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The advancement of HIV treatment has led to increased life expectancy. However, people living with HIV (PLWH) are at a higher risk of developing colorectal cancers. Chronic inflammation has a key role in oncogenesis, affecting the initiation, promotion, transformation, and advancement of the disease. PLWH are prone to opportunistic infections that trigger inflammation. It has been documented that 15-20% of cancers are triggered by infections, and this percentage is expected to be increased in HIV co-infections. The incidence of parasitic infections such as helminths, with Ascariasis being the most common, is higher in HIV-infected individuals. Cancer cells and opportunistic infections drive a cascade of inflammatory responses which assist in evading immune surveillance, making them survive longer in the affected individuals. Their survival leads to a chronic inflammatory state which further increases the probability of oncogenesis. This review discusses the key inflammatory signaling pathways involved in disease pathogenesis in HIV-positive patients with colorectal cancers. The possibility of the involvement of co-infections in the advancement of the disease, along with highlights on signaling mechanisms that can potentially be utilized as therapeutic strategies to prevent oncogenesis or halt cancer progression, are addressed.

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Gastric cancer (GC) is one of the major causes of cancer deaths worldwide. The disease is seldomly detected early and this limits treatment options. Because of its heterogeneous and complex nature, the disease remains poorly understood. The literature supports the contribution of the gut microbiome in the carcinogenesis and chemoresistance of GC. Drug resistance is the major challenge in GC therapy, occurring as a result of rewired metabolism. Metabolic rewiring stems from recurring genetic and epigenetic factors affecting cell development. The gut microbiome consists of pathogens such as H. pylori, which can foster both epigenetic alterations and mutagenesis on the host genome. Most of the bacteria implicated in GC development are Gram-negative, which makes it challenging to eradicate the disease. Gram-negative bacterium co-infections with viruses such as EBV are known as risk factors for GC. In this review, we discuss the role of microbiome-induced GC carcinogenesis. The disease risk factors associated with the presence of microorganisms and microbial dysbiosis are also discussed. In doing so, we aim to emphasize the critical role of the microbiome on cancer pathological phenotypes, and how microbiomics could serve as a potential breakthrough in determining effective GC therapeutic targets. Additionally, consideration of microbial dysbiosis in the GC classification system might aid in diagnosis and treatment decision-making, taking the specific pathogen/s involved into account.

Asunto(s)

Helicobacter pylori , Microbiota , Neoplasias Gástricas , Humanos , Metagenómica , Disbiosis/microbiología , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiología , Epigenómica , Recurrencia Local de Neoplasia , Microbiota/genética , Helicobacter pylori/genética , Carcinogénesis/patología

RESUMEN

Renal papillary necrosis (RPN) is characterized by coagulative necrosis of the renal medullary pyramids and papillae. Multiple conditions and toxins are associated with RPN. Several RPN risk factors, or POSTCARDS, have been identified, with most patients presenting with RPN having at least two contributing risk factors. Currently, there is no specific test to diagnose and confirm RPN; however, several imaging tools can be used to diagnose the condition. RPN is currently underdiagnosed in African populations, often with fatal outcomes. In African clinical settings, there is a lack of consensus on how to define and describe RPN in terms of kidney anatomy, pathology, endourology, epidemiology, the identification of African-specific risk factors, the contribution of oxidative stress, and lastly an algorithm for managing the condition. Several risk factors are unique to African populations including population-specific genetic factors, iatrogenic factors, viral infections, antimicrobial therapy, schistosomiasis, substance abuse, and hypertension (GIVASSH). Oxidative stress is central to both GIVASSH and POSTCARDS-associated risk factors. In this review, we present information specific to African populations that can be used to establish an updated consensual definition and practical grading system for radiologists, urologists, nephrologists, nuclear physicians, and pathologists in African clinical settings.