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Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, characterized by the accumulation of amyloid-beta (Aβ) plaques and neuroinflammation. This study investigates the protective effects of noradrenaline (NA) on human microglial cells exposed to lipopolysaccharides (LPS) and Aβ aggregates—major contributors to inflammation and cellular damage in AD. The reduced Aβ aggregation in the HMC3 human microglial cells co-treated with Aβ and NA was confirmed by thioflavin T (ThT) assay, fluorescent ThT staining, and immunocytochemistry (ICC). The significantly increased viability of HMC3 cells after 48 h of incubation with NA at 50 µM, 25 µM, and 10 µM, exposed to IC50 LPS and IC50 Aβ, was confirmed by XTT and LDH assays. Moreover, we found that NA treatment at 25 μM and 50 μM concentrations in HMC3 cells exposed to IC50 LPS or IC50 Aβ results in an increased proliferation of HMC3 cells, their return to normal morphology, decreased levels of DNA damage, reduced caspase-3 activity, decreased expression of pro-apoptotic DDIT3 and BAX, and increased expression of anti-apoptotic BCL-2 genes and proteins, leading to enhanced cell survival, when compared to that of the HMC3 cells treated only with IC50 LPS or IC50 Aβ. Furthermore, we showed that NA induces the degradation of both extracellular and intracellular Aβ deposits and downregulates hypoxia-inducible factor 1α (HIF-1α), which is linked to impaired Aβ clearance and AD progression. These findings indicate that NA holds promise as a therapeutic target to address microglial dysfunction and potentially slow the progression of AD. Its neuroprotective effects, particularly in reducing inflammation and regulating microglial activity, warrant further investigation into its broader role in mitigating neuroinflammation and preserving microglial function in AD. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common type of dementia worldwide. The etiopathogenesis of this disease remains unknown. Currently, several hypotheses attempt to explain its cause, with the most well-studied being the cholinergic, beta-amyloid (Aβ), and Tau hypotheses. Lately, there has been increasing interest in the role of immunological factors and other proteins such as alpha-synuclein (α-syn) and transactive response DNA-binding protein of 43 kDa (TDP-43). Recent studies emphasize the role of tunneling nanotubes (TNTs) in the spread of pathological proteins within the brains of AD patients. TNTs are small membrane protrusions composed of F-actin that connect non-adjacent cells. Conditions such as pathogen infections, oxidative stress, inflammation, and misfolded protein accumulation lead to the formation of TNTs. These structures have been shown to transport pathological proteins such as Aβ, Tau, α-syn, and TDP-43 between central nervous system (CNS) cells, as confirmed by in vitro studies. Besides their role in spreading pathology, TNTs may also have protective functions. Neurons burdened with α-syn can transfer protein aggregates to glial cells and receive healthy mitochondria, thereby reducing cellular stress associated with α-syn accumulation. Current AD treatments focus on alleviating symptoms, and clinical trials with Aβ-lowering drugs have proven ineffective. Therefore, intensifying research on TNTs could bring scientists closer to a better understanding of AD and the development of effective therapies. [ABSTRACT FROM AUTHOR]

Despite significant advancements in the field of oncology, cancers still pose one of the greatest challenges of modern healthcare. Given the cytoskeleton's pivotal role in regulating mechanisms critical to cancer development, further studies of the cytoskeletal elements could yield new practical applications. Septins represent a group of relatively well-conserved GTP-binding proteins that constitute the fourth component of the cytoskeleton. Septin 9 (SEPT9) has been linked to a diverse spectrum of malignancies and appears to be the most notable septin member in that category. SEPT9 constitutes a biomarker of colorectal cancer (CRC) and has been positively correlated with a high clinical stage in breast cancer, cervical cancer, and head and neck squamous cell carcinoma. SEPT9_i1 represents the most extensively studied isoform of SEPT9, which substantially contributes to carcinogenesis, metastasis, and treatment resistance. Nevertheless, the mechanistic basis of SEPT9_i1 oncogenicity remains to be fully elucidated. In this review, we highlight SEPT9's and SEPT9_i1's structures and interactions with Hypoxia Inducible Factor α (HIF-1 α) and C-Jun N-Terminal Kinase (JNK), as well as discuss SEPT9_i1's contribution to aneuploidy, cell invasiveness, and taxane resistance—key phenomena in the progression of malignancies. Finally, we emphasize forchlorfenuron and other septin inhibitors as potential chemotherapeutics and migrastatics. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disorder which affects dopaminergic neurons of the midbrain. Accumulation of α-synuclein or exposure to neurotoxins like 6-hydroxydopamine (6-OHDA) induces endoplasmic reticulum (ER) stress along with the unfolded protein response (UPR), which executes apoptosis via activation of PERK/CHOP or IRE1/JNK signaling. The present study aimed to determine which of these pathways is a major contributor to neurodegeneration in an 6-OHDA-induced in vitro model of PD. For this purpose, we have applied pharmacological PERK and JNK inhibitors (AMG44 and JNK V) in differentiated SH-SY5Y cells exposed to 6-OHDA. Inhibition of PERK and JNK significantly decreased genotoxicity and improved mitochondrial respiration, but only JNK inhibition significantly increased cell viability. Gene expression analysis revealed that the effect of JNK inhibition was dependent on a decrease in MAPK10 and XBP1 mRNA levels, whereas inhibition of either PERK or JNK significantly reduced the expression of DDIT3 mRNA. Western blot has shown that JNK inhibition strongly induced the XBP1s protein, and inhibition of each pathway attenuated the phosphorylation of eIF2α and JNK, as well as the expression of CHOP. Collectively, our data suggests that targeting the IRE1/JNK pathway of the UPR is a more effective option for PD treatment as it simultaneously affects more than one pro-apoptotic pathway. [ABSTRACT FROM AUTHOR]

Currently, an important group of biomaterials used in the research in the field of tissue engineering is thermosensitive chitosan hydrogels. Their main advantage is the possibility of introducing their precursors (sols) into the implantation site using a minimally invasive method—by injection. In this publication, the results of studies on the new chitosan structures in the form of thermosensitive hydrogels containing graphene oxide as a nanofiller are presented. These systems were prepared from chitosan lactate and chitosan chloride solutions with the use of a salt of pyrimidine nucleotide—uridine 5′-monophosphate disodium salt—as the cross-linking agent. In order to perform the characterization of the developed hydrogels, the sol–gel transition temperature of the colloidal systems was first determined based on rheological measurements. The hydrogels were also analyzed using FTIR spectroscopy and SEM. Biological studies assessed the cytotoxicity (resazurin assay) and genotoxicity (alkaline version of the comet assay) of the nanocomposite chitosan hydrogels against normal human BJ fibroblasts. The conducted research allowed us to conclude that the developed hydrogels containing graphene oxide are an attractive material for potential use as scaffolds for the regeneration of damaged tissues. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) represents the most common histological type of lung cancer, characterized by a five-year survival rate of 15% and poor prognosis. Accumulating evidence indicates a prominent role of endoplasmic reticulum (ER) stress and the protein kinase RNA-like ER kinase (PERK)-dependent pathway of the unfolded protein response (UPR) in the pathogenesis of NSCLC. Increased expression of downstream targets of PERK was observed in various subtypes of NSCLC, and it was associated with a more aggressive phenotype, high risk of recurrence, and poor prognosis. Therefore, the present study aimed to investigate the biological effect of the selective PERK inhibitor NCI 159456 on A549 NSCLC cells and Human Pulmonary Fibroblasts (HPF) in vitro. Treatment of both normal and ER-stressed A549 cells with NCI 159456 resulted in a significant increase in the mRNA expression level of pro-apoptotic genes like activating transcription factor 4 (ATF4), DNA damage inducible transcript 3 (DDIT3), and BCL2 Associated X, Apoptosis Regulator (BAX) as well as a decreased level of the anti-apoptotic gene B-cell lymphoma 2 (Bcl-2). Cytotoxicity and genotoxicity analyses revealed that NCI 159456 significantly decreased viability and increased DNA damage in A549 cells under normal and ER stress conditions. Caspase-3 and reactive oxygen species (ROS) detection assays demonstrated that NCI 159456 significantly induced apoptosis and increased the ROS level in normal and ER-stressed A549 cells. Importantly, treatment with the inhibitor did not affect substantially normal HPF cells at any used concentration. The results indicate that PERK inhibitors could potentially be applied as a targeted therapy for NSCLC. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a complex neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the substantia nigra and the widespread accumulation of alpha-synuclein (αSyn) protein aggregates. αSyn aggregation disrupts critical cellular processes, including synaptic function, mitochondrial integrity, and proteostasis, which culminate in neuronal cell death. Importantly, αSyn pathology extends beyond neurons—it also encompasses spreading throughout the neuronal environment and internalization by microglia and astrocytes. Once internalized, glia can act as neuroprotective scavengers, which limit the spread of αSyn. However, they can also become reactive, thereby contributing to neuroinflammation and the progression of PD. Recent advances in αSyn research have enabled the molecular diagnosis of PD and accelerated the development of targeted therapies. Nevertheless, despite more than two decades of research, the cellular function, aggregation mechanisms, and induction of cellular damage by αSyn remain incompletely understood. Unraveling the interplay between αSyn, neurons, and glia may provide insights into disease initiation and progression, which may bring us closer to exploring new effective therapeutic strategies. Herein, we provide an overview of recent studies emphasizing the multifaceted nature of αSyn and its impact on both neuron and glial cell damage. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative brain disease. Thus, drugs including donepezil, rivastigmine, and galantamine are not entirely effective in the treatment of this multifactorial disease. The present study evaluates eight derivatives (3a–3h) as candidates with stronger anti-AD potential but with less side effects. Reactive oxygen species (ROS) assays were used to assess oxidative stress which involve in the neurodegeneration. The neuroprotective properties of 3e against oxidative stress were done in three experiments using MTT test. The anti-AD potential was determined based on their anticholinesterase inhibition ability, determined using Ellman's method, Aβ aggregation potential according to thioflavin (Th) fluorescence assay, and their antioxidative and anti-inflammatory activities. Compound 3e exhibited moderate cholinesterase inhibition activity (AChE, IC50 = 0.131 µM; BuChE, IC50 = 0.116 µM; SI = 1.13), significant inhibition of Aβ(1–42) aggregation (55.7%, at 5 µM) and acceptable neuroprotective activity. Extensive analysis of in vitro and in vivo assays indicates that new cyclopentaquinoline derivatives offer promise as candidates for new anti-AD drugs. [ABSTRACT FROM AUTHOR]

Creating innovative methods of treatment and regeneration of damaged tissues or organs is a key challenge of the twenty-first century. The aim of this study was to determine the possibility of producing and characterising the properties of self-organising chitosan hydrogels prepared with the use of chitosan lactate/chloride and disodium hydrogen phosphate dodecahydrate as a cross-linking agent. The structure and supramolecular architecture of the biomaterials were evaluated by Fourier-transform infrared spectroscopy and polarised optical microscopy. Biological studies assessed cytotoxicity by contact with a human colon adenocarcinoma cell line. The colourimetric resazurin assay showed that the obtained chitosan hydrogels are non-cytotoxic materials. Thus, self-organising biomaterials hold great promise for application in tissue engineering. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most common neurodegenerative disorder in worldwide and remains a therapeutic challenge due to the low efficacy of current treatments. Numerous studies have demonstrated the pivotal role of endoplasmic reticulum (ER) stress in PD pathogenesis. ER stress, followed by activation of the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-dependent branch of the unfolded protein response signaling pathway, ultimately leads to neural cell death and dopaminergic neurodegeneration in PD. Therefore, the present study evaluated the effectiveness of the small-molecule PERK inhibitor LDN-87357 in an in vitro PD model using the human neuroblastoma SH-SY5Y cell line. To assess the mRNA expression levels of the pro-apoptotic ER stress markers, the TaqMan Gene Expression Assay was performed. Cytotoxicity was assessed using a colorimetric 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay and apoptosis was assessed using a caspase-3 assay. Moreover, cell cycle progression was evaluated using flow cytometry. The results indicated that LDN-87357 treatment induced a significant decrease in ER stress markers gene expression in SH-SY5Y cells exposed to ER stress. Furthermore, LDN-87357 significantly increased viability, diminished apoptosis and restored the normal cell cycle distribution of SH-SY5Y cells after ER stress induction. Therefore, the evaluation of small-molecule PERK inhibitors, such as LDN-87357, may lead to the development of novel therapeutic strategies against PD. [ABSTRACT FROM AUTHOR]

Wstęp: Reumatoidalne zapalenie stawów (RZS) jest wielogenową, wieloczynnikową i przewlekłą chorobą o podłożu immunologicznym, charakteryzującą się przewlekłym zapaleniem stawów, skłonnością do powstawania deformacji stawów oraz zajęciem tkanek pozastawowych. Ryzyko zachorowania na nowotwory złośliwe wśród pacjentów z RZS jest przedmiotem ciągłych badań ze względu na autoimmunologiczną patogenezę leżącą u podstaw RZS, wspólną etiologię choroby reumatycznej i nowotworów złośliwych oraz stosowanie terapii immunomodulacyjnej, która może zmieniać funkcjonowanie systemu odpornościowego i zwiększać tym samym ryzyko zachorowania na nowotwory złośliwe. Jedną z charakterystycznych cech RZS jest stres oksydacyjny, który powoduje zwiększony poziom uszkodzeń DNA w tkankach chorych z RZS. Czynnikiem genetycznym związanym z predyspozycją do inicjacji procesu transformacji nowotworowej może być polimorfizm genów kodujących białka biorące udział w systemach naprawy DNA. Zróżnicowanie form allelicznych danego genotypu może objawiać się różną aktywnością tych białek a przez to osobniczo-indywidualną zdolnością do naprawy uszkodzeń DNA. Cel: Celem naszych badań była ocena zmienności genetycznej w RZS w obrębie genów sytemu naprawy uszkodzeń DNA przez wycinanie zasad azotowych (BER), wycinania nukleotydów (NER) oraz system naprawy pęknięć dwuniciowych przez rekombinacje homologiczną (HR) i niehomologiczne łączenie końców (NHEJ). Materiały i Metody: Materiał do badań stanowił DNA izolowany z komórek PBMC 150 osób chorych na RZS i zdrowych. Genotypy polimorfizmów określano za pomocą Taq-man SNP Genotyping Assay. Przebadano łącznie 29 polimorfizmów dla 19 genów kodujących białka związane z naprawą DNA. Wyniki: Zaobserwowaliśmy związek między występowaniem RZS a polimorfizmami genów: XRCC2 (rs3218536) w modelu naddominującym dla genotypu C/T (OR 2.87; 95% CI 1.09-7.54), RAD51 (rs7180135) w modelu recesywnym dla genotypu A/A (OR 0.51; 95% CI 0.30-0.85) oraz modelu naddominującym dla genotypu A/G (OR 1.65; 95% CI 1.04-2.62), RAD51 (rs1801321) w modelu kodominującym dla genotypu T/T (OR 2.07; 95% CI 1.22-3.52), modelu recesywnym dla genotypu T/T (OR 2.15; 95% CI 1.35-3.42), RAD51B (rs963917) w modelu kodominującym dla genotypu A/A (OR 0.33; 95% CI 0.16-0.68), modelu dominującego dla genotypu A/G-A/A (OR 0.54; 95% CI 0.34-0.87), modelu recesywnym dla genotypu A/A (OR 95% 0.41; CI 0.21-0.81), RAD51B (rs963918) w modelu kodominującym dla genotypu T/T (OR 0.42; 95% CI 0.20-0.91), modelu recesywnym dla genotypu T/T (OR 0.55; 95% CI 0.35-0.88), NBN (rs2735383) w modelu kodominującym dla genotypu G/G (OR 0.29; 95% CI 0.10-0.86); modelu recesywnym dla genotypu G/G (OR 0.33; 95% CI 0.12-0.95), XRCC5 (rs207906) w modelu kodominującym dla genotypu A/G (OR 2.00; 95% CI 1.22-3.28), modelu dominującym dla genotypu A/G-A/A (OR 1.91; 95% CI 1.21-3.02), modelu naddominującym dla genotypu A/G (OR 1.83; 95% CI 1.14-2.95), TDG (rs4135054) w modelu kodominującym dla genotypu T/T (OR 0.11; 95% CI 0.01-0.86), w modelu dominującym dla genotypu C/T-T/T (OR 0.53; 95% CI (0.31-0.90) oraz modelu recesywnym dla genotypu T/T (OR 0.12; 95% CI 0.01-0.96). Podsumowanie: Nasze wyniki sugerują, że odpowiedź komórki na uszkodzenia DNA może odgrywać rolę w procesie patogenezy RZS, a polimorfizmy genów naprawy uszkodzeń DNA mogą być uważane za potencjalne markery RZS. [ABSTRACT FROM AUTHOR]

Wstęp: W patogenezie reumatoidalnego zapalenia stawów (RZS) odgrywają rolę trzy podstawowe czynniki: genetyczne, środowiskowe i autoimmunologiczne. Udział czynników genetycznych w rozwoju RZS szacuje się na 50-60%, a udział HLA w tym procesie na 10-40%. Badania asocjacyjne GWAS doprowadziły do zidentyfikowania wielu loci warunkujących podatność na zachorowanie na RZS. Jednymi z głównych polimorfizmów pojedynczych nukleotydów (SNPs) związanych z RZS są warianty alleliczne genów PADI4, TRAF1, STAT4, CD40 i PTPN22. Cel: Celem naszych badań była ocena zmienności genetycznej w RZS w obrębie genów PADI4, TRAF1, STAT4, CD40 i PTPN22 ryzyka związanych z sygnalizacją receptora komórek T z seropozytywnością. Materiały i Metody: Materiał do badań stanowił DNA izolowany z komórek PBMC 150 osób chorych na RZS i zdrowych. Genotypy polimorfizmów określano za pomocą Taq-man SNP Genotyping Assay. Przebadano łącznie 5 polimorfizmów dla genów PADI4 (RS2240340), TRAF1 (RS3761847), STAT4 (RS757486), CD40 (RS4810485) i PTPN22 (RS2476601). Wyniki: Zaobserwowaliśmy związek między występowaniem RZS a polimorfizmami genów: PADI4 (w modelu kodominującym C/T zwiększa iloraz szans RZS w populacji polskiej 3,5 krotnie (OR=3,54) T/T dwukrotnie (OR=2.00), oraz w modelu dominującym niemal 3 krotnie (OR=2.93), STAT4 (zwiększa iloraz szans RZS w populacji polskiej we wszystkich badanych modelach, w modelu kodominującym G/T dwukrotnie (OR=1.89) oraz T/T czterokrotnie (OR=4.07), w modelu dominującym dwukrotnie (OR=2.08) oraz w modelu recesywnym ponad 3 krotnie (OR=3.22)) i PTPN22 (zarówno w modelu kodominującym G/A (OR=1.82) jak i w modelu dominującym (OR=2.14) dwukrotnie zwiększa iloraz szans RZS w populacji polskiej). Polimorfizm genów TRAF1 i CD40 nie modulował ilorazu szans wystąpienia RZS w populacji polskiej. Podsumowanie: Wyniki te wskazują na znaczenie genów spoza układu HLA w określaniu ryzyka zachorowania na RZS w populacji polskiej. Związek wielu wariantów ryzyka związanych z sygnalizacją receptora komórek T z seropozytywnością może odgrywać istotną rolę w odmiennych fenotypach klinicznych RZS. [ABSTRACT FROM AUTHOR]

Wstęp: Reumatoidalne zapalenie stawów (RZS) jest chorobą stawów o podłożu autoimmunologicznym, o nieznanej jeszcze etiologii. RZS powoduje przewlekłe zapalenie tkanek stawowych, co powoduje destrukcję chrząstki stawowej i kości. Jedną z charakterystycznych cech RZS jest stres oksydacyjny, najprawdopodobniej indukowany i stymulowany przez nieprawidłową aktywność limfocytów B i T. Jak wykazaliśmy wcześniej, skutkuje to akumulacją oksydacyjnych uszkodzeń DNA w komórkach jednojądrzastych krwi obwodowej (PBMC) izolowanych od chorych na RZS. Postawiliśmy hipotezę, że stres oksydacyjny wraz z nieefektywną naprawą przez wycięcie zasad - BER może być odpowiedzialny za zwiększoną częstość występowania u chorych na RZS chłoniaków i raka płuc. Nieefektywny BER może być skutkiem występowania polimorfizmów genów białek BER oraz zmian epigenetycznych. Cel: Celem pracy była korelacja pomiędzy naprawą oksydacyjnych uszkodzeń DNA oraz tłem genetycznym i epigenetycznym. Materiały i Metody: Materiał do badań stanowiły komórki PBMC izolowane z krwi 30 chorych na RZS i 30 zdrowych osób. Uszkodzenia i naprawę DNA oceniano za pomocą elektroforezy w żelu alkalicznym pojedynczych komórek (test kometowy), genotypy polimorfizmów określano za pomocą Taq-man SNP Genotyping Assay, a profil ekspresji genów związanych z BER analizowano za pomocą Real Time qPCR Assay. Wyniki: Realizując cel pracy określiliśmy poziom oksydacyjnych uszkodzeń DNA oraz kinetykę naprawy uszkodzeń DNA indukowanych przez wodoronadtlenek tert-butylu (TBH) w PBMCs chorych na RZS i osób zdrowych. Wyniki badań uszkodzeń i naprawy DNA zostały skorelowane z genotypami polimorfizmów kluczowych genów BER oraz poziomem ich ekspresji. Zaobserwowaliśmy związek między występowaniem RZS, wrażliwością na TBH (OR 1,39; 95% CI, 1,18-1,65), nieprawidłową naprawą DNA w PBMCs (OR 46,00; 95% CI, 8,70-243,26), polimorfizmem genów XRCC1 (OR 6,07; 95% CI, 1,82-20,22) i MUTYH (OR 4,72; 95% CI, 1,54-14,52) a zmienioną ekspresją kluczowych genów BER. Podsumowanie: Nasze wyniki sugerują, że warianty genetyczne w obrębie genów BER, jak również czynniki epigenetyczne mogą być powiązane z RZS poprzez modulację odpowiedzi komórkowej na stres oksydacyjny. Ponadto polimorfizmy te mogą być użytecznym dodatkowym markerem w tej chorobie wraz z genetycznymi i/lub środowiskowymi wskaźnikami stresu oksydacyjnego. [ABSTRACT FROM AUTHOR]

<b> Introduction:</b> The newest data has reported that endoplasmic reticulum (ER) stress and PERK-dependent Unfolded Protein Response (UPR) signaling pathway may constitute a key factor in colorectal cancer (CRC) pathogenesis on the molecular level. Nowadays used anti-cancer treatment strategies are still insufficient, since patients suffer from various side effects that are directly evoked via therapeutic agents characterized by non-specific action in normal and cancer cells. </br></br> <b>Aim:</b> Thereby, the main aim of the presented research was to analyze the effectiveness of the small-molecule PERK inhibitor NCI 12487 in an in vitro cellular model of CRC. </br></br> <b>Materials and methods:</b> The study was performed on colorectal cancer HT-29 and normal human colon epithelial CCD 841 CoN cell lines. The cytotoxicity was measured by XTT assay, evaluation of apoptosis was performed by caspase-3 assay, whereas cell cycle analysis via the propidium iodide (PI) staining. </br></br> <b>Results:</b> Results obtained have demonstrated that the investigated compound is selective only for HT-29 cancer cells, since at 25 μM concentration it significantly decreased HT-29 cells viability in a dose- and time-dependent manner, evoked increased caspase-3 activity and arrest in the G2/M phase of the cell cycle. Moreover, NCI 12487 compound markedly decreased HT-29 cells viability, increased caspase-3 activity and percentage of cells in sub-G0/G1, thus promoted apoptosis of cancer HT-29 cells with induced ER stress conditions. </br></br> <b>Conclusion:</b> Thus, based on the results obtained in this study it may be concluded that small-molecule modulators of the PERK-dependent UPR signaling pathway may constitute an innovative, targeted treatment strategy against CRC.

<br><b>Aim:</b> Gem-associated protein 4 (GEMIN4), a member of the GEMIN gene family, is a key compound of the regulating factors responsible for miRNA biogenesis. Genetic variability within this gene can alter the risk for development of colorectal cancer (CRC) as was shown for other genes involved in miRNA biogenesis. Therefore, presented study was intended to identify genetic variants of three single nucleotide polymorphisms (SNPs) in the GEMIN4 gene (rs1062923, rs2740348 and rs910925) and their relationship with CRC.</br> <br><b>Methods:</b> The study comprised 203 patients and 179 age and sex matched controls. Genotyping of GEMIN4 gene variants was done using Taqman® assay. The association of GEMIN4 variants with CRC was done by odds ratio analysis. Haplotype analysis was done to see the combined effect of studied variants on CRC.</br> <br><b>Results:</b> Patients carrying all variant genotypes for GEMIN4 rs1062923 (odds ratio [OR]= 0.205; 95% confidence interval [CI] = 0.1034-0.4065 for CC variant and [OR] = 0.1436; [CI] = 0.0869-0.2373 for CT variant, respectively) and GEMIN4 rs2740348 (odds ratio [OR] = 0.4498; 95% confidence interval [CI] = 0.2342-0.8637 for CC variant and [OR] = 0.3986; [CI] = 0.2043-0.7776 for CG variant, respectively) showed significant association in lower occurrence of cancer, whereas in case of GEMIN4 G/C rs910925 variant genotype, no significance correlation was found.</br> <br><b>Conclusion:</b> Our study gives a substantive support for the association between the GEMIN4 gene variants/miRNA biogenesis and CRC risk.</br&gt.