21 research outputs found
An intricate rewiring of cancer metabolism via alternative splicing
No full textAll human genes undergo alternative splicing leading to the diversity of the proteins. However, in some cases, abnormal regulation of alternative splicing can result in diseases that trigger defects in metabolism, reduced apoptosis, increased proliferation, and progression in almost all tumor types. Metabolic dysregulations and immune dysfunctions are crucial factors in cancer. In this respect, alternative splicing in tumors could be a potential target for therapeutic cancer strategies. Dysregulation of alternative splicing during mRNA maturation promotes carcinogenesis and drug resistance in many cancer types. Alternative splicing (changing the target mRNA 3'UTR binding site) can result in a protein with altered drug affinity, ultimately leading to drug resistance.. Here, we will highlight the function of various alternative splicing factors, how it regulates the reprogramming of cancer cell metabolism, and their contribution to tumor initiation and proliferation. Also, we will discuss emerging therapeutics for treating tumors via abnormal alternative splicing. Finally, we will discuss the challenges associated with these therapeutic strategies for clinical applications
Alternative Splicing: A Potential Therapeutic Target in Hematological Malignancies
No full textLeukemia represents the most prevalent malignancy in children, constituting 30% of childhood cancer cases, with acute lymphoblastic leukemia (ALL) being particularly heterogeneous. This paper explores the role of alternative splicing in leukemia, highlighting its significance in cancer development and progression. Aberrant splicing is often driven by mutations in splicing-factor genes, which can lead to the production of variant proteins that contribute to oncogenesis. The spliceosome, a complex of small nuclear RNAs and proteins, facilitates RNA splicing, a process critical for generating diverse mRNA and protein products from single genes. Mutations in splicing factors, such as U2AF1, SF3B1, SRSF2, ZRSR2, and HNRNPH1, are frequently observed across various hematological malignancies and are associated with poor prognosis and treatment resistance. This research underscores the necessity of understanding the mechanisms of RNA splicing dysregulation in order to develop targeted therapies to correct these aberrant processes, thereby improving outcomes for patients with leukemia and related disorders
P53: A key player in diverse cellular processes including nuclear stress and ribosome biogenesis, highlighting potential therapeutic compounds
No full textThe tumor suppressor proteins are key transcription factors involved in the regulation of various cellular processes,such as apoptosis, DNA repair, cell cycle, senescence, and metabolism. The tumor suppressor protein p53 responds to different type of stress signaling, such as hypoxia, DNA damage, nutrient deprivation, oncogene activation, by activating or repressing the expression of different genes that target processes mentioned earlier. p53 has the ability to modulate the activity of many other proteins and signaling pathway through protein–protein interaction, post-translational modifications, or non-coding RNAs. In many cancers the p53 is found to be mutated or inactivated, resulting in the loss of its tumor suppressor function and acquisition of new oncogenic properties. The tumor suppressor protein p53 also plays a role in the development of other metabolic disorders such as diabetes, obesity, and fatty liver disease. In this review, we will summarize the current data and knowledge on the molecular mechanisms and the functions of p53 in different pathways and processes at the cellular level and discuss the its implications for human health and disease
Advances in molecular function of UPF1 in Cancer
No full textIt is known that more than 10% of genetic diseases are caused by a mutation in protein-coding mRNA (premature termination codon; PTC). mRNAs with an early stop codon are degraded by the cellular surveillance process known as nonsense-mediated mRNA decay (NMD), which prevents the synthesis of C-terminally truncated proteins. Up-frameshift-1 (UPF1) has been reported to be involved in the downregulation of various cancers, and low expression of UPF1 was shown to correlate with poor prognosis. It is known that UPF1 is a master regulator of nonsense-mediated mRNA decay (NMD). UPF1 may also function as an E3 ligase and degrade target proteins without using mRNA decay mechanisms. Increasing evidence indicates that UPF1 could serve as a good biomarker for cancer diagnosis and treatment for future therapeutic applications. Long non-coding RNAs (lncRNAs) have the ability to bind different proteins and regulate gene expression; this role in cancer cells has already been identified by different studies. This article provides an overview of the aberrant expression of UPF1, its functional properties, and molecular processes during cancer for clinical applications in cancer. We also discussed the interactions of lncRNA with UPF1 for cell growth during tumorigenesis
Ribosome-directed therapies in cancer
No full textThe human ribosomes are the cellular machines that participate in protein synthesis, which is deeply affected during cancer transformation by different oncoproteins and is shown to provide cancer cell proliferation and therefore biomass. Cancer diseases are associated with an increase in ribosome biogenesis and mutation of ribosomal proteins. The ribosome represents an attractive anti-cancer therapy target and several strategies are used to identify specific drugs. Here we review the role of different drugs that may decrease ribosome biogenesis and cancer cell proliferation
Ultrastructure of sertoli cells in cryptorchid goats
No full textPT: J; CR: AMAT P, 1985, J ANDROL, V6, P1 CHEMES HE, 1979, BIOL REPROD, V21, P241 CHEVALIER M, 1978, ANN BIOL ANIM BIOCH, V18, P1279 CLEGG EJ, 1963, J ENDOCRINOL, V26, P567 EZEASOR DN, 1985, J ANAT, V141, P27 EZEASOR DN, 1987, AM J VET RES, V48, P1736 HADZISELIMOVIC F, 1980, CLIN ANDROLOGY DESCE, V3, P163 HATIER R, 1980, ANAT EMBRYOL, V160, P11 JONES TM, 1977, ANAT REC, V189, P1 KERR JB, 1975, J REPROD FERTIL, V43, P1 KERR JB, 1979, BIOL REPROD, V21, P823 KOFF WC, 1988, SCIENCE, V241, P426 ROSS MH, 1975, ANAT REC, V183, P267 SCHULZE C, 1976, ANDROLOGIA, V8, P167 SINGH A, 1981, PATHOLOGY, V13, P487 SINGH A, 1989, DEV ULTRASTRUCTURE R, P159 SKINNER MK, 1985, J CELL BIOL, V100, P1941 TOYAMA Y, 1975, CELL TISSUE RES, V158, P205 TRAN D, 1982, ENDOCRINOLOGY, V111, P1562 VANVORSTENBOSCH CJ, 1984, BIOL REPROD, V31, P565; NR: 20; TC: 3; J9: ARCH ANDROLOGY; PG: 10; GA: AM133Source type: Electronic(1
Ribosome biogenesis and ribosome therapy in cancer cells
No full textIntroduction: The process of protein synthesis is a vital process for all kingdoms of life. The ribosome is a ribonucleoprotein complex that reads the genetic code, from messenger RNA (mRNA) to produce proteins and to tightly regulate and ensure cells growth. The fact that numerous diseases are caused by defect during the ribosome biogenesis is important to understand this pathway. Materials and methods: We have analyzed the literature for ribosome biogenesis and its links with different diseases which have been found. Results and discussion: We have discussed the key aspect of human ribosome biogenesis and its links to diseases. We have also proposed the potential of applying this knowledge to the development of a ribosomal stress-based cancer therapy. Conclusion: Major challenges in the future will be to determine factors which play a pivotal role during ribosome biogenesis. Therefore, more anti-cancer drugs and gene therapy for genetic diseases will be developed against ribosomal biogenesis in the coming years. Graphical abstract
Epigenetics and treatment of systemic lupus erythematosus
No full textSystemic lupus erythematosus (SLE) is a disease associated with an impaired autoimmune response; the immune system attacks erroneously own tissues, which leads to inflammation, tissue damage and complement activation. The latter plays a pivotal role in SLE pathology, as complement level is suited as histological marker for disease diagnoses and management. Besides, environmentally factors have been highlighted and their significant contribution for individual genetic predisposition has been pointed out. Here complement factors, their activity and their ability to modify DNA with histone proteins are reviewed; known gene mutations involved in SLE, and new therapeutic approaches suggested for SLE are discussed and summarized, as well
A PRELIMINARY STUDY OF THE PALEOLITHIC AND NEOLITHIC CONTRIBUTION THE EUROPEAN MTDNA FLOW IN SHAPING THE GENETIC STRUCTURE OF RECENT BOSNIAN POPULATION
No full textThe mitochondrial DNA (mtDNA) polymorphisms in Bosnian human population was analyzed by means of hypervariable segment I and II (HVSI and HVSII) sequencing and restriction fragment-length polymorphism analysis of the mtDNA coding region. The results suggest that shaping the genetic structure of recent Bosnian population likely to be affected by the expansion from the European glacial refuges area at the end of the Last Glacial Maximum (LGM), postglacial expansions from southwestern refuges of Europe, the Italian Peninsula and the dispersion in periods of more recent historical events, from the East European Plain. Especially interesting feature of the Neolithic expansion in this area is the ancient African/South Asian haplogroup N1a with the HVSI variant 16147G, which is almost absent in Europe. The haplotyps HVSI with variant 16147G suggest the colonization of the Northeast Bosnia region by Neolithic communities in the Early Neolithic period of expansion through Europe, as evidenced by the archaeological remains of the Starcevo culture
