Colorectal Cancer Cell Proliferation Research Articles

SNORA28 Promotes Proliferation and Radioresistance in Colorectal Cancer Cells through the STAT3 Pathway by Increasing H3K9 Acetylation in the LIFR Promoter.

Radiotherapy is essential for treating colorectal cancer (CRC), especially in advanced rectal cancer. However, the low radiosensitivity of CRC cells greatly limits radiotherapy efficacy. Small nucleolar RNAs (snoRNAs) are a class of noncoding RNA that primarily direct post-transcriptional modifications of ribosomal RNAs (rRNAs), small nuclear RNAs (snRNAs), and other cellular RNAs. While snoRNAs are involved in tumor progression and chemoresistance, their association with radiosensitivity remains largely unknown. Herein, SNORA28 is shown highly expressed in CRC and is positively associated with poor prognosis. Furthermore, SNORA28 overexpression enhances the growth and radioresistance of CRC cells in vitro and in vivo. Mechanistically, SNORA28 acts as a molecular decoy that recruits bromodomain-containing protein 4 (BRD4), which increases the level of H3K9 acetylation at the LIFR promoter region. This stimulates LIFR transcription, which in turn triggers the JAK1/STAT3 pathway, enhancing the proliferation and radioresistance of CRC cells. Overall, these results highlight the ability of snoRNAs to regulate radiosensitivity in tumor cells and affect histone acetylation modification in the promoter region of target genes, thus broadening the current knowledge of snoRNA biological functions and the mechanism underlying target gene regulation.

Aberrant Expression of Sprouty2 In Human Colon Cancer

Purpose: The study investigates the role of Sprouty2 (SPRY2) in colorectal cancer (CRC) cell function. It found that SPRY2 inhibits the RAS/MAPK/ERK pathway and promotes cancer invasion in KRAS-WT CRC. However, it did not significantly alter p-ERK levels, cell proliferation, or invasion in KRAS-mutant CRCs. High SPRY2 expression was associated with shorter cancer-specific survival in both KRAS-WT and KRAS-mutant CRC patients. The study suggests that SPRY2 may promote invasion and progression in both types of CRC. Methods: The gene expression data were retrieved from Gene Expression Omnibus (GEO). Fold change, p.value t-test and David Functional analysis, hierarchical clustering was performed. Results: In this study, we identified altered genes involved in SPRY2 mutation in the colon and the relevant pathways to understand whether the SPRY2 mutation changes cancer progression. 4 genes of 5 genes were downregulated following the mutation in colon cancer cells. We identified a network between these genes and pathways they belong to. Pathway analysis showed that these genes are mostly associated with cancer cell proliferation. Conclusion: MAL2, ESRP1, CDH3, CXCL14 and CDH1 genes were found to be associated with in SPRY2 mutation in colon cancer pathogenesis. Almost all these genes are effective in the proliferation of cancer cells, especially during the SPRY2 mutation process. Therefore, it is hypothesized that downregulation or upregulation of these genes may affect colon cancer pathogenesis by reducing cell proliferation. And it is predicted that SPRY2 mutation may be an important factor for colon cancer.

Circ_0000518 regulates miR-326/EPHB3 axis to promote colorectal cancer progression

BackgroundCircular RNAs (circRNAs) have emerged as potential clinical targets in cancer therapy, since they have been shown to play a crucial role in tumor development by acting as competitive endogenous RNAs (ceRNAs) that regulate downstream mRNA expression by sequestering microRNAs (miRNAs). The present study, aimed to identify novel ceRNA networks involving circRNAs, miRNAs, and mRNAs in using a combination of Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets and explore the function of circ_0000518 in the malignancy of colorectal cancer (CRC). MethodsRaw data related to CRC, including circRNAs, miRNAs and mRNAs, were downloaded from GEO and TCGA databases. A circRNA/miRNA/mRNA network was established by differential analysis and multiple databases were used to predict downstream targets. The role of this network in the development of CRC was further validated by a series of cellular experiments including dual luciferase assay, migration assay and flow apoptosis assay. ResultsDifferential expression analysis of two GEO datasets (GSE142837 and GSE126094) revealed four circRNAs, which were used to predict downstream miRNAs and mRNAs based on several databases. These predictions, combined with TCGA analysis, were used to construct a ceRNA network composed of 4 circRNAs, 9 miRNAs, and 52 mRNAs. The circ_0000518/miR-326/ephrin type-B receptor 3 (EPHB3) axis was eventually selected for functional validation in two CRC cell lines. Subsequently, it was experimentally verified that circ_0000518 was highly expressed in CRC; meanwhile, it was found that the proliferation and migration of CRC cells were significantly weakened by knocking down circ_0000518, while apoptosis of tumors was promoted. ConclusionThe data demonstrated the identification of a novel circRNA/miRNA/mRNA competitive endogenous network in CRC. The regulatory role of the circ_0000518/miR-326/EPHB3 axis in this network was preliminarily validated by cellular experiments exploring CRC tissue samples and two CRC cell lines.

Development, Optimization, and in vitro Evaluation of Silybin-loaded PLGA Nanoparticles and Decoration with 5TR1 Aptamer for Targeted Delivery to Colorectal Cancer Cells.

Chemotherapeutic agents often lack specificity, intratumoral accumulation, and face drug resistance. Targeted drug delivery systems based on nanoparticles (NPs) mitigate these issues. Poly (lactic-co-glycolic acid) (PLGA) is a well-studied polymer, commonly modified with aptamers (Apts) for cancer diagnosis and therapy. In this study, silybin (SBN), a natural agent with established anticancer properties, was encapsulated into PLGA NPs to control delivery and improve its poor solubility. The field-emission scanning electron microscopy (FE-SEM) showed spherical and uniform morphology of optimum SBN-PLGA NPs with 138.57±1.30nm diameter, 0.202±0.004 polydispersity index (PDI), -16.93±0.45mV zeta potential (ZP), and 70.19±1.63% entrapment efficiency (EE). The results of attenuated total reflectance-Fourier transform infrared (ATR-FTIR) showed no chemical interaction between formulation components, and differential scanning calorimetry (DSC) thermograms confirmed efficient SBN entrapment in the carrier. Then, the optimum formulation was functionalized with 5TR1 Apt for active targeted delivery of SBN to colorectal cancer (CRC) cells in vitro. The SBN-PLGA-5TR1 nanocomplex released SBN at a sustained and constant rate (zero-order kinetic), favoring passive delivery to acidic CRC environments. The MTT assay demonstrated the highest cytotoxicity of the SBN-PLGA-5TR1 nanocomplex in C26 and HT29 cells and no significant cytotoxicity in normal cells. Apoptosis analysis supported these results, showing early apoptosis induction with SBN-PLGA-5TR1 nanocomplex which indicated this agent could cause programmed death more than necrosis. This study presents the first targeted delivery of SBN to cancer cells using Apts. The SBN-PLGA-5TR1 nanocomplex effectively targeted and suppressed CRC cell proliferation, providing valuable insights into CRC treatment without harmful effects on healthy tissues.

CLK3 positively promoted colorectal cancer proliferation by activating IL-6/STAT3 signaling

Colorectal cancer (CRC) poses a significant challenge in oncology due to its increasing global incidence and treatment complexities. This study delved into the role of the dual-specificity protein kinase CLK3 in CRC progression and its potential as a therapeutic target. By analyzing clinical data and experimental models comprehensively, we found that CLK3 expression was markedly elevated in CRC tissues compared to normal colon tissue. High CLK3 levels were associated with advanced clinical stages and poor prognosis in CRC patients, suggesting its utility as a prognostic biomarker. Functional assays demonstrated that CLK3 overexpression boosted CRC cell proliferation and ATP production, whereas genetic CLK3 knockdown hindered cell proliferation in vitro and curbed tumor growth in vivo. Mechanistically, we uncovered that CLK3 positively influenced the IL-6/STAT3 signaling pathway by stabilizing JAK2 protein levels. These findings propose targeting CLK3 signaling as a promising therapeutic approach for CRC. Further investigation into CLK3's molecular mechanisms and clinical implications is necessary to fully harness its potential in managing CRC.

Exploring Butein’s anticancer potential in colorectal cancer: Insights into proliferation inhibition, apoptosis induction, and metastasis suppression via p38 signaling

BackgroundButein, a natural chalcone found in plants, exhibits promising anti-tumor effects across cancers, yet its role in Colorectal cancer (CRC) remain largely unclear. MethodsWe utilized pharmacological, molecular, and in vivo models to assess its impact on CRC cell proliferation, apoptosis, migration, and invasion. Molecular docking and network pharmacology analyses predicted potential target proteins and pathways regulated by Butein. Experimental validations included western blotting, immunohistochemistry, and functional assays. ResultsButein significantly inhibited CRC cell proliferation, induced apoptosis, and disrupted the epithelial-mesenchymal transition (EMT). Its repression of cell migration and invasion capabilities, suggesting potential anti-metastatic properties. The activation of the p38 signaling pathway emerged as a key mechanism mediating Butein’s anti-tumor effects, supported by network pharmacology predictions and experimental evidence. ConclusionThis study highlights the multifaceted anti-cancer potential of Butein in CRC, emphasizing its promising application and the novel role of the p38 pathway.

Saikosaponin D Inhibits Lung Metastasis of Colorectal Cancer Cells by Inducing Autophagy and Apoptosis.

Saikosaponin D (SSD), derived from Bupleurum falcatum L., has various pharmacological properties, including immunoregulatory, anti-inflammatory, and anti-allergic effects. Several studies have investigated the anti-tumor effects of SSD on cancer in multiple organs. However, its role in colorectal cancer (CRC) remains unclear. Therefore, this study aimed to elucidate the suppressive effects of SSD on CRC cell survival and metastasis. SSD reduced the survival and colony formation ability of CRC cells. SSD-induced autophagy and apoptosis in CRC cells were measured using flow cytometry. SSD treatment increased LC3B and p62 autophagic factor levels in CRC cells. Moreover, SSD-induced apoptosis occurred through the cleavage of caspase-9, caspase-3, and PARP, along with the downregulation of the Bcl-2 family. In the in vivo experiment, a reduction in the number of metastatic tumor nodules in the lungs was observed after the oral administration of SSD. Based on these results, SSD inhibits the metastasis of CRC cells to the lungs by inducing autophagy and apoptosis. In conclusion, SSD suppressed the proliferation and metastasis of CRC cells, suggesting its potential as a novel substance for the metastatic CRC treatment.

Urolithin C suppresses colorectal cancer progression via the AKT/mTOR pathway

Urolithin families are gut-microbial metabolites of ellagic acid (EA). Although urolithin A (UA) and urolithin B (UB) were reported to have antiproliferative activities in cancer cells, the role and related mechanisms of urolithin C (UC) in colorectal cancer (CRC) have not yet been clarified. In this study, we assess the antitumor activities of UC in vitro and in vivo and further explore the underlying mechanisms in CRC cell lines. We found that UC inhibited the proliferation and migration of CRC cells, induced apoptosis, and arrested the cell cycle at the G2/M phase in vitro, and UC inhibited tumor growth in a subcutaneous transplantation tumor model in vivo. Mechanically, UC blocked the activation of the AKT/mTOR signaling pathway by decreasing the expression of Y-box binding protein 1(YBX1). The AKT agonist SC79 could reverse the suppression of cell proliferation in UC-treated CRC cells. In conclusion, our research revealed that UC could prevent the progression of CRC by blocking AKT/mTOR signaling, suggesting that it may have potential therapeutic values.Graphical

Curcumin suppresses colorectal cancer by induction of ferroptosis via regulation of p53 and solute carrier family 7 member 11/glutathione/glutathione peroxidase 4 signaling axis.

Driven by iron-dependent lipid peroxidation, ferroptosis is regulated by p53 and solute carrier family 7 member 11 (SLC7A11)/glutathione/glutathione peroxidase 4 (GPX4) axis in colorectal cancer (CRC). This study aimed to investigate the influence of curcumin (CUR) on ferroptosis in CRC. The efficacies of CUR on the malignant phenotype of CRC cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, wound healing, and clonogenic assays. The effects of CUR on ferroptosis of CRC cells were evaluated by transmission electron microscopy, lactate dehydrogenase release assay, Fe2+ staining, and analyses of reactive oxygen species, lipid peroxide, malondialdehyde, and glutathione levels. CUR's targets in ferroptosis were predicted by network pharmacological study and molecular docking. With SW620 xenograft tumors, the efficacy of CUR on CRC was investigated, and the effects of CUR on ferroptosis were assessed by detection of Fe2+, malondialdehyde, and glutathione levels. The effects of CUR on expressions of p53, SLC7A11, and GPX4 in CRC cells and tumors were analyzed by quantitative reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry. CUR suppressed the proliferation, migration, and clonogenesis of CRC cells and xenograft tumor growth by causing ferroptosis, with enhanced lactate dehydrogenase release and Fe2+, reactive oxygen species, lipid peroxide, and malondialdehyde levels, but attenuated glutathione level in CRC. In silico study indicated that CUR may bind p53, SLC7A11, and GPX4, consolidated by that CUR heightened p53 but attenuated SLC7A11 and GPX4 mRNA and protein levels in CRC. CUR may exert an inhibitory effect on CRC by inducing ferroptosis via regulation of p53 and SLC7A11/glutathione/GPX4 axis.

Comprehensive analysis of the relationship between ubiquitin-specific protease 21 (USP21) and prognosis, tumor microenvironment infiltration, and therapy response in colorectal cancer

BackgroundUbiquitin-specific proteases family is crucial to host immunity against pathogens. However, the correlations between USP21 and immunosurveillance and immunotherapy for colorectal cancer (CRC) have not been reported.MethodsThe differential expression of USP21 between CRC tissues and normal tissues was analyzed using multiple public databases. Validation was carried out in clinical samples through qRT-PCR and IHC. The correlation between USP21 and the prognosis, as well as clinical pathological characteristics of CRC patients, was investigated. Moreover, cell models were established to assess the influence of USP21 on CRC growth and progression, employing CCK-8 assays, colony formation assays, and wound-healing assays. Subsequently, gene set variation analysis (GSVA) was used to explore the potential biological functions of USP21 in CRC. The study also examined the impact of USP21 on cytokine levels and immune cell infiltration in the tumor microenvironment (TME). Finally, the effect of USP21 on the response to immunotherapy and chemotherapy in CRC was analyzed.ResultsThe expression of USP21 was significantly upregulated in CRC. High USP21 is correlated with poor prognosis in CRC patients and facilitates the proliferation and migration capacities of CRC cells. GSVA indicated an association between low USP21 and immune activation. Moreover, low USP21 was linked to an immune-activated TME, characterized by high immune cell infiltration. Importantly, CRC with low USP21 exhibited higher tumor mutational burden, high PD-L1 expression, and better responsiveness to immunotherapy and chemotherapeutic drugs.ConclusionThis study revealed the role of USP21 in TME, response to therapy, and clinical prognosis in CRC, which provided novel insights for the therapeutic application in CRC.

Therapeutic Applications of Nanoformulated Resveratrol and Quercetin Phytochemicals in Colorectal Cancer-An Updated Review.

Natural compounds such as polyphenols play several positive roles in maintaining the oxidative and inflammatory capacity of cells, which leads to their potential use as anticancer therapeutics. There is promising evidence for the in vitro and in vivo anticancer activity of many polyphenols, including resveratrol and quercetin, specifically in the treatment of colorectal cancer (CRC). There is a clear association between resveratrol and quercetin in interfering with the mechanistic pathways involved in CRC, such as Wnt, P13K/AKT, caspase-3, MAPK, NF-κB, etc. These molecular pathways establish the role of resveratrol and quercetin in controlling cancer cell growth, inducing apoptosis, and inhibiting metastasis. The major bottleneck in the progression of the use of resveratrol and quercetin as anticancer therapeutics is their reduced bioavailability in vivo because of their rapid metabolism in humans. Recent advancements in various nanotechnological formulations are promising for overcoming these bioavailability issues. Various nanoformulations of resveratrol and quercetin have shown an optimistic impact on reducing the solubility and improving the stability of resveratrol and quercetin in vivo. A combinatorial approach using nanoformulations of resveratrol with quercetin could potentially increase the impact of resveratrol in controlling CRC cell proliferation. This review discusses the mechanism of resveratrol and quercetin, the two bioactive polyphenolics, in colon cancer, with an emphasis on various types of nanoformulations of the two molecules targeting colon cancer. It also explores the synergistic effect of combining resveratrol and quercetin in various nanoformulations, targeting colon cancer. This research delves into the enhanced pharmacokinetics and potential chemotherapeutic benefits of these bioactive polyphenolics when used together in innovative ways.

Regulation of Metastasis and Growth of Colorectal Cancer via Targeting the PTEN Pathway: An Update on the Progress of LncRNA MLLT4-AS1.

Globally, colorectal cancer (CRC) is known as the primary cause of mortality. Recent studies have reported that long non-coding RNAs (lncRNAs) are essential in assessing the survival of CRC patients. However, the function of the novel lncRNA MLLT4-AS1 in CRC is still unknown. This study aimed to identify the expression and the clinical significance of lncRNA MLLT4-AS1 in CRC. The level of MLLT4-AS1 in CRC was evaluated via the TCGA database. The relative level of MLLT4-AS1 in CRC cell lines was assessed by RT qPCR analysis. In cell culture, HT29 cells were transfected with MLLT4-AS1 siRNA, negative control, overexpressed MLLT4-AS1, or PTEN plasmids. Flow cytometry, CCK 8 assay, wound healing analysis, and transwell assay were used to quantify apoptosis, cell propagation, migration, and invasion, respectively. A nude mouse xenograft model was developed to evaluate the in vivo impact of MLLT4-AS1 plasmids on tumor growth. RNA pull-down analysis was used to search for possible targets of MLLT4-AS1. MLLT4-AS1 was substantially increased in CRC cell lines and patients. It inhibited CRC cell apoptosis and accelerated their proliferative, migration, and invasive properties. In in vivo analysis, MLLT4-AS1 also enhanced the metastasis and proliferation of CRC cells. It was found that PTEN was substantially enriched by biotin-labeled PTEN, as identified via an RNA pull-- down analysis. The expression of phosphatase and PTEN was suppressed by MLLT4-AS1 by ubiquitination proteasome-dependent RNA degradation. Thus, PTEN is considered a potential target of MLLT4-AS1. By targeting PTEN, MLLT4-AS1 intensified the biological behavior of malignant CRC. The study concluded that the MLLT4-AS1/PTEN axis may represent an innovative therapeutic intervention for CRC patients.

Guanine-Rich RNA Sequence Binding Factor 1 Deficiency Promotes Colorectal Cancer Progression by Regulating PI3K/AKT Signaling Pathway.

Guanine-rich RNA sequence binding factor 1 (GRSF1), part of the RNA-binding protein family, is now attracting interest due to its potential association with the progression of a variety of human cancers. The precise contribution and molecular mechanism of GRSF1 to colorectal cancer (CRC) progression, however, have yet to be clarified. Immunohistochemistry and Western Blot analysis was carried out to detect the expression of GRSF1 in CRC at both mRNA and protein levels and its subsequent effects on prognosis. A series of functional tests were performed to understand its influence on proliferation, migration, and invasion of CRC cells. The universal downregulation of GRSF1 in CRC was identified, indicating a correlation with poor prognosis. Our functional studies unveiled that the elimination of GRSF1 enhances tumour activities such as proliferation, migration, and invasion of CRC cells, while GRSF1 overexpression curtailed these abilities. Notably, we uncovered that GRSF1 insufficiency modulates the PI3K/Akt signaling pathway and Ras activation in CRC. Therefore, our data suggest GRSF1 operates as a tumor suppressor gene in CRC and may offer promise as a potential biomarker and novel therapeutic target in CRC management.

High glucose inhibits autophagy and promotes the proliferation and metastasis of colorectal cancer through the PI3K/AKT/mTOR pathway.

Colorectal cancer (CRC) ranks among the most prevalent malignancies worldwide, characterized by its complex etiology and slow research progress. Diabetes, as an independent risk factor for CRC, has been widely certified. Consequently, this study centers on elucidating the intricacies of CRC cells initiation and progression within a high-glucose environment. A battery of assays was employed to assess the proliferation and metastasis of CRC cells cultured under varying glucose concentrations. Optimal glucose levels conducive to cells' proliferation and migration were identified. Western blot analyses were conducted to evaluate alterations in apoptosis, autophagy, and EMT-related proteins in CRC cells under high-glucose conditions. The expression of PI3K/AKT/mTOR pathway-associated proteins was assessed using western blot. The effect of high glucose on xenograft growth was investigated invivo by MC38 cells, and changes in inflammatory factors (IL-4, IL-13, TNF-α, IL-5, and IL-12) were measured via serum ELISA. Our experiments demonstrated that elevated glucose concentrations promoted both the proliferation and migration of CRC cells; the most favorable glucose dose is 20 mM. Western blot analyses revealed a decrease in apoptotic proteins, such as Bim, Bax, and caspase-3 with increasing glucose levels. Concurrently, the expression of EMT-related proteins, including N-cadherin, vimentin, ZEB1, and MMP9, increased. High-glucose cultured cells exhibited elevated levels of PI3K/AKT/mTOR pathway proteins. In the xenograft model, tumor cells stimulated by high glucose exhibited accelerated growth, larger tumor volumes, and heightened KI67 expression of immunohistochemistry. ELISA experiments revealed higher expression of IL-4 and IL-13 and lower expression of TNF-α and IL-5 in the serum of high-glucose-stimulated mice. The most favorable dose and time for tumor cells proliferation and migration is 20 mM, 48 h. High glucose fosters CRC cell proliferation and migration while suppressing autophagy through the activation of the PI3K/AKT/mTOR pathway.

Application and evaluation of fecal SDC2 gene methylation in the diagnosis and treatment of colorectal cancer.

e15541 Background: SDC2 gene encodes the transmembrane proteoglycan molecule Syndecan-2. Syndecan-2 protein affects the proliferation, migration and invasion of colorectal cancer cells by regulating cell adhesion, tissue differentiation and angiogenesis. The aim of this study is to verify the sensitivity and specificity of fecal SDC2 gene methylation in the detection of colorectal cancer, find the dominant population who can benefit from this detection, expand its clinical application scenarios, and explore its role in the evaluation of the efficacy and prognosis of patients with advanced colorectal cancer. Methods: A total of 72 patients diagnosed with colorectal cancer were included in the study. The methylation level of SDC2 gene in feces of patients was detected by fluorescence PCR. We evaluated sensitivity and specificity and assessed associations between fecal SDC2 methylation levels, fecal occult blood tests, characteristics of the lesions on colonoscopy, and clinical practice. The critical value of reaction solution A was 10.0, and the critical value of reaction solution B was 10.5. When the Ct value of any tube of reaction solution A or B was less than the critical value, it was judged as "positive". Results: Data from 72 patients were evaluated, with a sensitivity of 89.1% (41/46 95%CI 0.798 to 0.985) for patients with untreated colorectal cancer. The sensitivity of SDC2 methylation detection was 46.2% (12/26 95%CI 0.256-0.667) in patients with partial response or stable disease after palliative treatment. The difference in the detection rate of SDC2 methylation between the two groups was statistically significant (P < 0.001). Among the 46 untreated patients with colorectal cancer, 32 patients with positive SDC2 gene methylation received radical surgery, and 30 of them (93.75%) turned to SDC2 gene methylation negative after surgery. Patients who achieved clinical benefit (CR+PR+SD) found reduced SDC2 gene methylation levels in the stool.There was no significant difference in the methylation level of SDC2 gene between colorectal cancer patients with different fecal occult blood test results (-, +, ++, +++) (P = 0.564)、different lesions (ascending colon, transverse colon , descending colon , sigmoid colon, and rectal) (P = 0.179)、different stages (stage I, II, III, IV) (P = 0.828)、different types (infiltrative, ulcerative, protruding) (P = 0.629), and different sizes of lesions (≤ 5cm, 6-9cm, ≥10cm) (P = 0.644). Conclusions: The high sensitivity of fecal SDC2 gene methylation in detecting untreated CRC patients may help make colonoscopy a screening method only for those at high risk of developing CRC. It may help to evaluate the efficacy of radical surgery, predict the recurrence of colorectal cancer and monitor the efficacy of palliative treatments for colorectal cancer. This work was supported by Shanghai Shenkang Project (No.SHDC2022CRT009).

Mechanism of Spica Prunellae in Suppressing Proliferation and Stem Cell Properties of Colorectal Cancer Cells Based on Notch Signaling Pathway

Mechanism of Spica Prunellae in Suppressing Proliferation and Stem Cell Properties of Colorectal Cancer Cells Based on Notch Signaling Pathway

Role of dietary nutrients and metabolism in colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignancies and the leading causes of cancer related deaths worldwide. The development of CRC is driven by a combination of genetic and environmental factors. There is growing evidence that changes in dietary nutrition may modulate the CRC risk, and protective effects on the risk of developing CRC have been advocated for specific nutrients such as glucose, amino acids, lipid, vitamins, micronutrients and prebiotics. Metabolic crosstalk between tumor cells, tumor microenvironment components and intestinal flora further promote proliferation, invasion and metastasis of CRC cells and leads to treatment resistance. This review summarizes the research progress on CRC prevention, pathogenesis, and treatment by dietary supplementation or deficiency of glucose, amino acids, lipids, vitamins, micronutri-ents, and prebiotics, respectively. The roles played by different nutrients and dietary crosstalk in the tumor microenvironment and metabolism are discussed, and nutritional modulation is inspired to be beneficial in the prevention and treatment of CRC.

The Role of Matrix Metalloproteinase-2 (MMP2) in Colorectal Cancer Progression: Correlation With Clinicopathological Features and Impact on Cellular Processes.

Background Colorectal cancer (CRC) is a prevalent and deadly disease characterized by significant molecular complexity. Matrix metalloproteinase-2 (MMP2) has been implicated in cancer progression due to its role in extracellular matrix degradation, yet comprehensive studies linking MMP2 expression to CRC progression and its molecular mechanisms remain needed. Methodology This study involved 90 CRC patients, with tumor and adjacent normal tissues analyzed via immunohistochemistry (IHC) to assess MMP2 expression. The human CRC cell line SW480 was treated with an MMP2 inhibitor, ARP100, and evaluated for changes in cell migration, invasion, proliferation, and apoptosis using various assays, including MTT, wound-healing, transwell, caspase activity, and western blot analysis. Results High MMP2 expression was significantly associated with advanced tumor stages, lymph node involvement, and metastasis in CRC patients. Compared to normal tissues, MMP2 expression was markedly higher in cancerous tissues. Inhibition of MMP2 in SW480 cells resulted in reduced migration, invasion, and proliferation, and induced apoptosis, evidenced by increased caspase 3 and 9 activities and higher levels of cleaved caspase proteins. Conclusion Elevated MMP2 expression is correlated with advanced CRC and aggressive tumor characteristics. MMP2 inhibition can suppress CRC cell invasiveness, migration, and proliferation while promoting apoptosis, suggesting its potential as a therapeutic target in CRC treatment.

Extracellular vesicles isolated from curcumin-medium weakened RKO cell proliferation and migration.

Curcumin (Cur) is a natural phytochemical that is expected to become an indispensable drug for the treatment of colorectal cancer. A comprehensive understanding of the anti-tumor mechanism of Cur will provide a better reference for its clinical application. This study aimed to examine the effects of extracellular vesicles (EVs) isolated from Cur-medium on RKO colorectal cancer cell proliferation, apoptosis, and migration. RKO cells were cultured in various concentrations of Cur-medium, and the EVs were isolated from the Cur-medium. The EVs were identified by transmission electron microscopy and western blotting. The effects of the EVs on RKO cell proliferation, apoptosis, and migration were analyzed, as was the expression of proliferating cell nuclear antigen (PCNA), Bax, vimentin, and E-cadherin. The expression of nuclear factor κB (NF-κB) p65 in the EVs was also detected. Our results showed that the EVs isolated from the Cur-medium weakened RKO cell proliferation and migration but had no effect on cell apoptosis. Cur suppressed the expression of NF-κB p65 in the EVs. Overall, this study revealed that Cur exerts anti-tumor effects by suppressing NF-κB p65 in EVs to weaken RKO cell proliferation and migration. In conclusion, the packaging of Cur into EVs is expected to become an indispensable treatment of colorectal cancer in the future.

LncRNA PVT1 facilitates the growth and metastasis of colorectal cancer by sponging with miR-3619-5p to regulate TRIM29 expression.

Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide. Long noncoding RNA (lncRNA) is involved in many malignant tumors. This study aimed to clarify the role of the lncRNA plasmacytoma variant translocation 1 (PVT1) in CRC growth and metastasis. Differentially expressed lncRNAs in CRC were analyzed using the Cancer Genome Atlas. Gene expression profiling interactive analysis and a comprehensive resource for lncRNAs from cancer arrays databases were used to analyze lncRNA PVT1 expression and CRC prognosis, respectively. Cell counting kit-8, wound healing, colony formation, Transwell, and immunofluorescence assays were used to evaluate CRC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), respectively. Tumor growth and metastasis models were used to explore the PVT1 effect on the growth and metastasis of CRC in vivo. PVT1 was highly expressed in CRC, associated with a poor prognosis of CRC, and showed good diagnostic value. Transfection of sh-PVT1 or pcDNA3.1-PVT1 reduced or increased the proliferation, wound healing rate, colony formation, invasion, and EMT of CRC cells. PVT1 and miR-3619-5p were co-expressed in CRC cytoplasm, and PVT1 acted as a competitive endogenous RNA (ceRNA) by sponging miR-3619-5p to up-regulate tripartite motif containing 29 (TRIM29) expression. MiR-3619-5p overexpression and TRIM29 knockdown reduced proliferation, wound healing rate, invasion, and EMT of CRC cells. However, simultaneous PVT1 and miR-3619-5p overexpression or knockdown of miR-3619-5p and TRIM29 knockdown rescued the malignant phenotype of CRC cells. We first clarified the ceRNA mechanism of PVT1 in CRC, which induced growth and metastasis by sponging with miR-3619-5p to regulate TRIM29.