Colon Cancer Proliferation Research Articles

The significance of homeodomain transcription factor 2 in colon cancer cells

BackgroundColon cancer is a serious malignant tumor. It has been reported that paired-like homeodomain transcription factor 2 (PITX2) can promote the progression of several types of cancer via regulating the Wnt/β-catenin pathway. It has also been demonstrated that high levels of long non-coding RNA (lncRNA) gastric carcinoma high expressed transcript 1 (GHET1) can also promote the development of cervical cancer via activating the Wnt/β-catenin pathway. However, whether PITX2 can affect the development of colon cancer via regulating the expression of lncRNA GHET1 remains unclear.ResultsThe results demonstrated that PITX2 knockdown attenuated the proliferation, migration and invasion abilities of colon cancer cells. Additionally, PITX2 promoted the expression of lncRNA GHET1 via binding to its promoter. Overexpression of lncRNA GHET1 induced the expression of Wnt/β-catenin signaling-related proteins, cyclin D1, c-Myc and MMP-7. Furthermore, lncRNA GHET1 overexpression abrogated the PITX2 silencing-mediated decreased proliferation, migration and invasion abilities of colon cancer cells.ConclusionThe findings of the present study suggested that PITX2 could enhance the proliferation, migration and invasion abilities of colon cancer cells via upregulating lncRNA GHET1 and activating the Wnt/β-catenin pathway.

Decreased Levels of Microfibril-Associated Glycoprotein (MAGP)-1 in Patients with Colon Cancer and Obesity Are Associated with Changes in Extracellular Matrix Remodelling

Objective: The protein microfibril-associated glycoprotein (MAGP)-1 constitutes a crucial extracellular matrix protein. We aimed to determine its impact on visceral adipose tissue (VAT) remodelling during obesity-associated colon cancer (CC). Methods: Samples obtained from 79 subjects (29 normoponderal (NP) (17 with CC) and 50 patients with obesity (OB) (19 with CC)) were used in the study. Circulating concentrations of MAGP-1 and its gene expression levels (MFAP2) in VAT were analysed. The impact of inflammation-related factors and adipocyte-conditioned media (ACM) on MFAP2 mRNA levels in colon adenocarcinoma HT-29 cells were further analysed. The effects of MAGP-1 in the expression of genes involved in the extracellular matrix (ECM) remodelling and tumorigenesis in HT-29 cells was also explored. Results: Obesity (p < 0.01) and CC (p < 0.001) significantly decreased MFAP2 gene expression levels in VAT whereas an opposite trend in TGFB1 mRNA levels was observed. Increased mRNA levels of MFAP2 after the stimulation of HT-29 cells with lipopolysaccharide (LPS) (p < 0.01) and interleukin (IL)-4 (p < 0.01) together with a downregulation (p < 0.05) after hypoxia mimicked by CoCl2 treatment was observed. MAGP-1 treatment significantly enhanced the mRNA levels of the ECM-remodelling genes collagen type 6 α3 chain (COL6A3) (p < 0.05), decorin (DCN) (p < 0.01), osteopontin (SPP1) (p < 0.05) and TGFB1 (p < 0.05). Furthermore, MAGP-1 significantly reduced (p < 0.05) the gene expression levels of prostaglandin-endoperoxide synthase 2 (COX2/PTGS2), a key gene controlling cell proliferation, growth and adhesion in CC. Interestingly, a significant decrease (p < 0.01) in the mRNA levels of MFAP2 in HT-29 cells preincubated with ACM from volunteers with obesity compared with control media was observed. Conclusion: The decreased levels of MAGP-1 in patients with obesity and CC together with its capacity to modulate key genes involved in ECM remodelling and tumorigenesis suggest MAGP-1 as a link between AT excess and obesity-associated CC development.

Significant Gene Biomarker Tyrosine Kinase Non-receptor 2 Mediated Cell Proliferation and Invasion in Colon Cancer.

Objective: This study aimed to investigate the expression and biological functions of TNK2 and miR-125a-3p in colon cancer.Materials and methods: The expression of TNK2 and miR-125a-3p in colon cancer tissues was analyzed using data deposited on public databases including UALCAN and ONCOMINE. We verified their expression in colon cancer cell lines by RT-qPCR and western blotting. By regulating the expression of TNK2 and miR-125a-3p in colon cancer cells, their functions and potential mechanisms were explored.Results:TNK2 was overexpressed in colon cancer cell lines, and it was found to directly bind to miR-125a-3p, which was downregulated in these cell lines. Their expression affected the proliferation and invasion of colon cancer cells. Additionally, colon cancer patients with lower TNK2 expression had better prognoses than those with higher TNK2 expression.Conclusion: Our results indicated that TNK2 and miR-125a-3p play critical roles in colon cancer, and could also serve as biomarkers for the diagnosis and prognosis of this malignant disease.

PHLDA1 expression in ulcerative colitis: A potential role in the management of dysplasia.

Pleckstrin homology-like domain, family A, member 1 (PHLDA1) is a protein involved in cell proliferation, adhesion and migration in colon cancer. In normal large intestinal mucosa, this protein is expressed only in the crypts. By contrast, its expression in adenomas and cancers of the large intestine is spread throughout the glandular ducts, and it has been reported that PHLDA1 may be involved in the process of carcinogenesis. PHLDA1 may also be involved in the pathogenesis of ulcerative colitis (UC). The expression levels of PHLDA1 in tissues from patients with UC were analyzed using immunohistochemistry, and its relationship with the development of UC-associated colorectal cancer (UC-CRC) was examined. Overall, tissue samples from 143 lesions (90 colitis lesions, 39 dysplastic lesions and 14 UC-CRC lesions) were prepared from excised specimens of 49 patients with UC who underwent surgery in Tokyo Medical and Dental University Hospital between January 2004 and December 2017. Subsequently, immunostaining for PHLDA1 was performed. PHLDA1 expression was evaluated in UC-CRC and dysplastic tissues within the entire lesion area on the slide and in colitis over the area of the accompanying duct. The cytoplasmic staining intensity was classified into four levels, and the expression score (0-2 points) was calculated. The median PHLDA1 expression score was 0.295 for colitis, 0.607 for dysplasia and 0.865 for UC-CRC. The dysplasia expression score was significantly higher than the colitis score (P<0.001), while the UC-CRC expression score was significantly higher than the dysplasia score (P=0.003). The expression levels of PHLDA1 in UC cases were higher in colitis, followed by dysplasia and UC-CRC, which suggested that this protein may be involved in the carcinogenesis of UC-CRC. In addition, PHLDA1 immunostaining may help in the diagnosis of dysplasia, which is a type of precancerous lesion.

RNA sequencing identified novel target genes for Adansonia digitata in breast and colon cancer cells.

Adansonia digitata exhibits numerous beneficial effects. In the current study, we investigated the anti-cancer effects of four different extracts of A. digitata (polar and non-polar extracts of fruit powder and fibers) on the proliferation of human colon cancer (HCT116), human breast cancer (MCF-7), and human ovarian cancer (OVCAR-3 and OVCAR-4) cell lines. RNA sequencing revealed the influence of the effective A. digitata fraction on the gene expression profiles of responsive cells. The results indicated that only the polar extract of the A. digitata fibers exhibited anti-proliferative activities against HCT116 and MCF-7 cells, but not ovarian cancer cells. Moreover, the polar extract of the fibers resulted in the modulation of the expression of multiple genes in HCT116 and MCF-7 cells. We propose that casein kinase 2 alpha 3 (CSNK2A3) is a novel casein kinase 2 (CSNK2) isoform in HCT116 cells and report, for the first time, the potential involvement of FYVE, RhoGEF, and PH domain-containing 3 (FGD3) in colon cancer. Together, these findings provide evidence supporting the anti-cancer potential of the polar extract of A. digitata fibers in this experimental model of breast and colon cancers.

Multiple myeloma driving factor WHSC1 is a transcription target of oncogene HMGA2 that facilitates colon cancer proliferation and metastasis

Colon cancer is a common human cancer worldwide. The survival rate of late staged or metastatic colon cancer patients remains low even though the effectiveness of treatment in colon cancer has greatly improved. Research on tumorigenesis mechanisms and discovery of novel molecular target for treating colon cancer is critical.The promotion roles of WHSC1 in multiple myeloma have been demonstrated previously, yet, the regulation of WHSC1 in other cancers is largely unknown, especially in colon cancer. Here, in this study, we analyzed and identified WHSC1 while studying the genetic regulations of HMGA2 in colon cancer cells by microarray analysis, and investigated the HMGA2-WHSC1 interaction. We then applied CRISPR technology to establish stable WHSC1 knockout cells, to address the functional regulation of WHSC1 in colon cancer. In summary, our results for the first time identified the HMGA2-WHSC1 interaction in colon cancer. Moreover, we discovered that WHSC1 promotes cancer proliferation, facilitates resistance of chemotherapy agent, and promotes metastatic capacity of colon cancer.

The Novel Curcumin Derivative 1g Induces Mitochondrial and ER-Stress-Dependent Apoptosis in Colon Cancer Cells by Induction of ROS Production.

Reactive oxygen species (ROS) play an important role in cellular metabolism. Many chemotherapeutic drugs are known to promote apoptosis through the production of ROS. In the present study, the novel curcumin derivative, 1g, was found to inhibit tumor growth in colon cancer cells both in vitro and in vivo. Bioinformatics was used to analyze the differentially expressed mRNAs. The mechanism of this effect was a change in mitochondrial membrane potential caused by 1g that increased its pro-apoptotic activity. In addition, 1g produced ROS, induced G1 checkpoint blockade, and enhanced endoplasmic reticulum (ER)-stress in colon cancer cells. Conversely, pretreatment with the ROS scavenging agent N-acetyl-l-cysteine (NAC) inhibited the mitochondrial dysfunction caused by 1g and reversed ER-stress, cell cycle stagnation, and apoptosis. Additionally, pretreatment with the p-PERK inhibitor GSK2606414 significantly reduced ER-stress and reversed the apoptosis induced by colon cancer cells. In summary, the production of ROS plays an important role in the destruction of colon cancer cells by 1g and demonstrates that targeted strategies based on ROS represent a promising approach to inhibit colon cancer proliferation. These findings reveal that the novel curcumin derivative 1g represents a potential candidate therapeutics for the treatment of colon cancer cells, via apoptosis caused by mitochondrial dysfunction and endoplasmic reticulum stress.

MicroRNA‑142‑3p suppresses cell proliferation, invasion and epithelial‑to‑mesenchymal transition via RAC1‑ERK1/2 signaling in colorectal cancer.

Aberrant expression of microRNAs (miRNAs/miRs) is associated with the initiation and progression of colorectal cancer (CRC), but how they regulate colorectal tumorigenesis is still unknown. The present study was designed to investigate the expression profile of miRNAs in human CRC tissues, and to reveal the molecular mechanism of miRNA-142-3p in suppressing colon cancer cell proliferation. The expression of miRNA was examined using an Exiqon miRNA array. Bioinformatics was used to predict the target genes of differentially expressed miRNAs and to analyze their biological function in CRC. The effect of miR-142-3p in colon cancer cells was evaluated in vitro using cell proliferation, colony formation and Transwell assays. Dual-luciferase reporter gene assays were performed to investigate the association between miR-142-3p and Rac family small GTPase 1 (RAC1). The effect of miR-142-3p regulation on colon cancer proliferation was assessed through western blotting and quantitative polymerase chain reaction analysis. Compared with their expression in adjacent non-cancer mucosal tissues, 76 miRNAs were upregulated and 102 miRNAs were downregulated in CRC. One of the most significantly and differentially regulated miRNAs was miR-142-3p, which was downregulated in 81.0% (51/63) of primary CRC tissues. After transfection of miR-142-3p mimics into colon cancer cells, proliferation and colony formation were decreased, and migration and invasion were markedly suppressed. RAC1 was a possible target of miR-142-3p, which was confirmed by dual-luciferase reporter assay. Transfection of miR-142-3p mimics decreased the levels of RAC1 and suppressed epithelial-to-mesenchymal transition in colon cancer cells. The phosphorylation of extraceullar signal-regulated kinase (ERK) was decreased significantly by the inhibition of RAC1 or transfection of miR-142-3p mimics in colon cancer cells. In conclusion, aberrant miRNAs are implicated in CRC. Decreased expression of miR-142-3p may be associated with CRC tumorigenesis via Rac1-ERK signaling.

Study on effects of miR-141-3p in proliferation, migration, invasion and apoptosis of colon cancer cells by inhibiting Bcl2.

This study aimed to investigate the relationship between miR-141-3p and B lymphocyte-2 gene (Bcl2) gene and its biological behavior on colon cancer cell line SW480. qRT-PCR was used to detect the expression level of miR-141-3p in colon cancer tissues and adjacent tissues, as well as in colon cancer cell line and normal human colonic epithelial cell line FHC. MTT assay, wound assay, and Transwell demonstrated the effects of miR-141-3p on colon cancer proliferation, migration and invasion. Targetscan7.1 predictive software and dual luciferase reporter assays were used to detect the targeted regulation of miR-141-3p on the apoptosis-related gene Bcl2. MTT assay, wound assay, Transwell and flow cytometry were used to detect the effect of Bcl2 on miR-141-3p on colon cancer proliferation, migration, invasion and apoptosis. Compared with adjacent tissues, the expression of miR-141-3p in colon cancer tissues was significantly down-regulated. Colon cancer patients with low expression of miR-141-3p had poorer prognosis. Compared with normal colonic epithelial cells, miR-141-3p expression was significantly down-regulated in colon cancer cell lines, and overexpression of miR-141-3p significantly attenuated the proliferation, migration and invasion of colon cancer cells. Knockdown of miR-141-3p significantly promoted the proliferation, migration and invasion of colon cancer cells. miR-141-3p targets the negative regulation of Bcl2. Knockdown of Bcl2 significantly attenuated the promotion of miR-141-3p inhibitor on proliferation, migration and invasion of colon cancer cells and inhibition of apoptosis. Knockdown of Bcl2 significantly enhanced the inhibition effect of miR-141-3p inhibitor on proliferation, migration and invasion of colon cancer cells. In conclusion, miR-141-3p can inhibit the cancer by regulating Bcl2, and miR-141-3p has the potential to become a potential therapeutic target for colon cancer.

The value of miR-510 in the prognosis and development of colon cancer.

PurposeColon cancer is one of the malignant tumors that threatens human health. miR-510 was demonstrated to play roles in the progression of various cancers; its dysregulation was speculated to be associated with the development of colon cancer.MethodsOne hundred and thirteen colon cancer patients participated in this research. With the help of RT-qPCR, the expression of miR-510 in collected tissues and cultured cells was analyzed. The association between miR-510 expression level and clinical features and prognosis of patients was evaluated. Moreover, the effects of miR-510 on cell proliferation, migration, and invasion of colon cancer were assessed by CCK8 and Transwell assay.ResultsmiR-510 significantly upregulated in colon cancer tissues and cell lines relative to the adjacent normal tissues and colonic cells. The expression of miR-510 was significantly associated with the TNM stage and poor prognosis of patients, indicating miR-510 was involved in the disease progression and clinical prognosis of colon cancer. Additionally, the upregulation of miR-510 significantly promoted cell proliferation, migration, and invasion of colon cancer, while its knockdown significantly inhibited these cellular processes. SRCIN 1 was the direct target of miR-510 during its promoted effect on the development of colon cancer.ConclusionThe upregulation of miR-510 acts as an independent prognostic indicator and a tumor promoter by targeting SRCIN 1 in colon cancer, which provides novel therapeutic strategies for colon cancer.

Galectin‑9 suppresses the tumor growth of colon cancer invitro and invivo.

Colon cancer is the second leading cause of cancer-related mortality worldwide, and the prognosis of advanced colon cancer has remained poor in recent years. Galectin-9 (Gal-9) is a tandem-repeat type galectin that has recently been shown to exert antiproliferative effects on various types of cancer cells. The present study aimed to assess the effects of Gal-9 on human colon and colorectal cancer cells in vitro and in vivo, as well as to evaluate the microRNAs (miRNAs/miRs) associated with the antitumor effects of Gal-9. We examined the ability of Gal-9 to inhibit cell proliferation via apoptosis, and the effects of Gal-9 on cell cycle-related molecules in various human colon and colorectal cancer cell lines. In addition, Gal-9-mediated changes in activated tyrosine kinase receptors and angiogenic molecules were assessed using protein array chips in colon and colorectal cancer cells. Moreover, miRNA array analysis was performed to examine Gal-9-induced miRNA expression profiles. We also elucidated if Gal-9 inhibited tumor growth in a murine in vivo model. We found that Gal-9 suppressed the cell proliferation of colon cancer cell lines in vitro and in vivo. Our data further revealed that Gal-9 increased caspase-cleaved keratin 18 levels in Gal-9-treated colon cancer cells. In addition, Gal-9 enhanced the phosphorylation of ALK, DDR1, and EphA10 proteins. Furthermore, the miRNA expression levels, such as miR-1246, miR-15b-5p, and miR-1237, were markedly altered by Gal-9 treatment in vitro and in vivo. In conclusion, Gal-9 suppresses the cell proliferation of human colon cancer by inducing apoptosis, and these findings suggest that Gal-9 can be a potential therapeutic target in the treatment of colon cancer.

Gallic acid suppresses colon cancer proliferation by inhibiting SRC and EGFR phosphorylation.

The aim of the present study was to investigate the effects of gallic acid (GA) on the proliferation and apoptosis of colon cancer cells and to further clarify the mechanism of GA function associated with SRC and EGFR phosphorylation. HCT116 and HT29 cells were treated with different concentrations of GA for 24 h. Cell proliferation and apoptosis were analyzed using plate clone formation and flow cytometry assays, respectively. In addition, the expression of apoptosis-related proteins was examined by western blotting. Furthermore, the level of STAT3, AKT, SRC and EGFR phosphorylation was analyzed by western blotting and immunofluorescence. Subsequently, the SRC inhibitor PP2 and the EGFR inhibitor gefitinib were used to analyze the GA-associated mechanisms. In addition, a xenograft tumor model was established to confirm the effects of GA in vivo. The results indicated that GA inhibited cell proliferation and promoted cell apoptosis by upregulating the ratio of cleaved caspase-3/pro-caspase-3 and cleaved caspase-9/pro-caspase-9. Concurrently, GA decreased the level of phosphorylated (p)-SRC, p-EGFR, p-AKT and p-STAT3. Following treatment with PP2 and gefitinib in both cancer cell lines and animal model, GA was demonstrated to inhibit EGFR and SRC phosphorylation to downregulate STAT3 and AKT phosphorylation. In vivo, GA prevented tumor growth, promoted tumor apoptosis and decreased the level of p-SRC, p-EGFR, p-STAT3 and p-AKT. In conclusion, GA was indicated to suppress colon cancer proliferation by inhibiting SRC and EGFR phosphorylation.

MiR-1253, a novel tumor suppressor gene in colon cancer, is associated with poor patients prognosis

MiR-1253 has been reported to play vital roles in a variety of cancers. However, its function in the progression and prognosis of colon cancer remains unclear. Here, the clinical significance and biological function of miR-1253 in the development of colon cancer was investigated. The expression of miR-1253 was identified in colon cancer tissues and cell lines by qRT-PCR. The prognostic value of miR-1253 was evaluated by Kaplan-Meier and Cox regression analysis. The roles of miR-1253 in regulating cell proliferation, migration, and invasion of colon cancer were evaluated in vitro by CCK8 and Transwell assay. It was found that miR-1253 was significantly downregulated in colon cancer tissues and cell lines (P < 0.001). The downregulation of miR-1253 was associated with the TNM stage (P = 0.007) and lymph node metastasis (P = 0.037) of patients. MiR-1253 (HR factor = 2.564, 95% CI = 1.077-6.107, P = 0.033) and TNM stage (HR factor = 2.899, 95% CI = 1.024-8.205, P = 0.045) were identified as independent factors that can predict the prognosis of patients. Functionally, miR-1253 acts as a tumor suppressor that inhibited cell proliferation, migration, and invasion of colon cancer through targeting EZH2. MiR-1253 was identified as a prognostic biomarker and a tumor suppressor of colon cancer.

Preparation and Preliminary Evaluation of Neurotensin Radiolabelled with 68Ga and 177Lu as Potential Theranostic Agent for Colon Cancer.

The neurotensin is a tridecapeptide involved in the proliferation of colon cancer, the overexpression of neurotensin receptors occurring at an early stage development of many tumours. Targeting neurotensin receptors by using the same biological active molecule is an effective approach for both imaging quantification and treatment. The present work aimed to demonstrate the ability of radiolabelled neurotensin to specifically target colon cancer cells, and substantiate its usefulness in targeted imaging and radiotherapy, depending on the emission of the coupled radioisotope. Syntheses of 68Ga–DOTA–NT and 177Lu–DOTA–NT were developed to obtain a level of quality suitable for preclinical use with consistent high synthesis yields. Radiochemical purity meets the pharmaceutical requirements, and it is maintained 4 h for 68Ga–DOTA–NT and 48 h for 177Lu–DOTA–NT. Extensive in vitro studies were conducted to assess the uptake and retention of 68Ga–DOTA–NT, the amount of non-specific binding of neurotensin and the effect of 177Lu–DOTA–NT on HT–29 cells. In vivo biodistribution of 68Ga–DOTA–NT revealed significant uptake at the tumour site, along with fast clearance evidenced by decreasing activity in kidneys and blood after 60 min p.i. 177Lu–DOTA–NT exhibited similar uptake in the tumour, but also a significant uptake at 14 days p.i. in the bone marrow was reported. These results successfully demonstrated the potential of neurotensin to deliver imaging/therapeutic 68Ga/177Lu radioisotopes pair, but also the need for further evaluation of the possible radiotoxicity effects on the liver, kidneys or bone marrow.

Pseudouridylate Synthase 7 Promotes Cell Proliferation and Invasion in Colon Cancer Through Activating PI3K/AKT/mTOR Signaling Pathway.

Colorectal cancer is commonly malignant tumor. Herein, we demonstrate that pseudouridylate synthase 7 (PUS7) is closely related to colon cancer. But the biological role of PUS7 in colon cancer is not known. The present study aims to investigate the effects of PUS7 in colon cancer clinical samples and cells and the related molecular mechanism. A profile data set was downloaded from the Cancer Genome Atlas database, which included data from colon cancer tissue samples and normal tissue samples. The top 200 differentially expressed genes were subsequently investigated by a protein-protein interaction (PPI) network. RT-PCR and western blot assays were used to determine gene expression levels. CCK8 assay, colony formation experiment, transwell and flow cytometry assay were used to determine cell viability, proliferation, invasion, and apoptosis, respectively. PUS7 is a key gene from the most significant module of the PPI network. PUS7 was upregulated in colon cancer tissues and cell lines. Moreover, PUS7 overexpression is significantly related to the poor survival rate for 60 colon cancer's patients. Cell proliferation and invasion was significantly reduced by PUS7 inhibition and promoted by PUS7 overexpression. The protein levels of cleaved caspase-3/9, c-myc, E-cadherin and vimentin genes were significantly regulated in colon cancer cells transfected with PUS7 interference or overexpression. PUS7 overexpression significantly upregulated the phosphorylation levels of PI3K, AKT and mTOR. The results of this study demonstrate thatPUS7 overexpression upregulates cell proliferation, invasion and inhibits cell apoptosis of colon cancer cells via activating PI3K/AKT/mTOR signaling pathway.

LncRNA AGAP2-AS1 Promotes Cancer Cell Proliferation, Migration and Invasion in Colon Cancer by Forming a Negative Feedback Loop with LINC-PINT.

IntroductionIt has been reported that lncRNA AGAP2-AS1 promotes the development of gastric cancer, lung cancer and breast cancer. This study aimed to investigate the role of AGAP2-AS1 in colon cancer.MethodsA total of 66 patients with colon cancer were enrolled. RT-qPCR was performed to detect the differential expression of AGAP2-AS1 in tumor tissues and adjacent normal tissues. To test the interaction between AGAP2-AS1 and LINC-PINT in colon cancer, overexpression vector or inhibitor of AGAP2-AS1 and LINC-PINT were transfected into RKO and HCT 116 cells. CCK-8 assay was used to detect cell proliferation. Transwell assays were performed to evaluate cell migration and invasion. The expression of p-LATS1, p-YAP and nuclear YAP were detected by Western blot and immunofluorescence.ResultsThe expression of AGAP2-AS1 was upregulated in colon cancer tissues compared with that in adjacent normal tissues, and the expression of AGAP2-AS1 in colon cancer tissues was not significantly affected by tumor stages. In addition, we found that the expression of LINC-PINT was downregulated in colon cancer tissues compared with that in adjacent normal tissues and had a reverse correlation with the expression of AGAP2-AS1 in colon cancer tissues. Moreover, overexpression of AGAP2-AS1 downregulated the expression of LINC-PINT, and overexpression of LINC-PINT also altered the expression of AGAP2-AS1 in colon cancer cells. Inhibition of AGAP2-AS1 upregulated the expression of LINC-PINT, and inhibition of LINC-PINT promoted the expression levels of AGAP2-AS1 in colon cancer cells. Furthermore, overexpression of AGAP2-AS1 could increase the proliferation, invasion and migration of colon cancer cells, while overexpression of LINC-PINT could attenuate the effects of overexpression of AGAP2-AS1 on the proliferation, migration and invasion of colon cancer cells. We also found that AGAP2-AS1 promoted colon cancer cell proliferation, migration and invasion through the Hippo signaling.ConclusionUpregulated expression of AGAP2-AS1 promoted proliferation, invasion and migration in colon cancer by forming a negative feedback loop with LINC-PINT.

A Triptolide Loaded HER2-Targeted Nano-Drug Delivery System Significantly Suppressed the Proliferation of HER2-Positive and BRAF Mutant Colon Cancer.

BackgroundColon cancer (CRC) was a malignant tumor and there were about 25% of patients with tumor metastasis at diagnosis stage. Chemotherapeutic agents for metastatic CRC patients were with great side effects and the clinical treatment results of advanced CRC were still not satisfactory. Human epidermal growth factor receptor 2 (HER2) is overexpressed in some CRC patients and is an effective target for CRC patient treatment. Anti-HER2 therapy had a beneficial role in the treatment of HER2-positive metastatic CRC with fewer side effects. CRC patients with BRAF mutations were resistant to HER2 antibodies treatment. Therefore, there was an urgent need to develop new therapeutic agents.MethodsHER2 targeted nanoparticles (TPLNP) drug delivery system loading triptolide (TPL) were prepared and identified. The effects of TPLNP and free TPL on cell viability, targeting and cell cycle progression on HT29 (BRAF mutation) with HER2 overexpression, were evaluated by Cell Counting Kit-8 (CCK8), Fluorescence Activating Cell Sorter (FACS) and immunofluorescence methods, respectively. The anti-tumor efficacies of TPLNP were evaluated in subcutaneous xenograft model of colon cancer and the survival rate, tumor volume, liver and kidney indexes of tumor-bearing mice were measured.ResultsTPLNP was small in nanosize (73.4±5.2nm) with narrow size distribution (PDI=0.15±0.02) and favorable zeta potential (pH=9.6, zeta potential: −57.3±6.69mV; pH=7.0, zeta potential: −28.7±5.1mV; pH=5.6, zeta potential: −21.1±4.73mV). Comparing with free TPL treatment group, TPLNP developed stranger colon cancer-killing efficiency in a dose- and time-dependent manner detected with CCK8 method; achieved good in vitro colon cancer targeting detected with flow cytometry and immunofluorescence experiments; enhanced more HT29-HER2 apoptosis and induced more cell cycle arrested in G1-S phase detected with FACS in vitro. As for in vivo antitumor response, TPLNP remarkably inhibited the growth of colon cancer in the colon cancer xenograft model, significantly improved the survival rate and did not exhibit significant liver and kidney toxicity in contrast with free TPL in vivo.ConclusionTPLNP was effectively against colon cancer with HER2 overexpression and BRAF mutation in pre-clinical models. In summary, the TPLNP appeared to be a promising treatment option for CRC in clinical application based on improved efficacy and the favorable safety profile.

Novel lncRNA LINC00941 Promotes Proliferation and Invasion of Colon Cancer Through Activation of MYC.

PurposeWe conducted the study to elucidate how LncRNA LINC00941 affects colon cancer progression and its possible regulatory mechanism.MethodsThe expression level of LINC00941 in colon cancer tissues and cells was detected by qRT-PCR. The function of LINC00941 on colon cancer cell proliferation, migration, and invasion was detected by CCK-8 and Transwell assay respectively. The target interactions among LINC00941, miR-205-5p, and MYC were further confirmed by dual-luciferase reporter gene assays and RNA pull-down experiments. Meanwhile, in vivo experiments were carried out to study the role of LINC00941 in the xenotransplantation model.ResultsLINC00941 expression level was elevated in colon cancer tissues and cells. LINC00941 overexpression accelerated proliferation, migration, and invasion of colon cancer cells, while the LINC00941 knockdown showed the opposite results. In addition, LINC00941 regulated the expression of MYC by sponging miR-205-5p as a competitive endogenous RNA, and miR-205-5p knockdown reversed the tumor inhibition of LINC00941 knockdown on colon cancer cells. Xenograft model assay confirmed that LINC00941 silencing could inhibit colon cancer cell growth and metastasis.ConclusionLINC00941 may markedly promote colon cancer progression by acting on the miR-205-5p/MYC axis as a ceRNA, which offers novel clues for lncRNA to guide the treatment and prognosis of colon cancer.

Possible Roles of Interleukin-4 and -13 and Their Receptors in Gastric and Colon Cancer.

Interleukin (IL)-4 and -13 are structurally and functionally related cytokines sharing common receptor subunits. They regulate immune responses and, moreover, are involved in the pathogenesis of a variety of human neoplasms. Three different receptors have been described for IL-4, but only IL-4 receptor type II (IL-4Rα/IL-13Rα1) is expressed in solid tumors. While IL-13 can also bind to three different receptors, IL-13 receptor type I (IL-4Rα/IL-13Rα1/IL-13Rα2) and type II (IL-4Rα/IL-13Rα1) are expressed in solid tumors. After receptor binding, IL-4 and IL-13 can mediate tumor cell proliferation, survival, and metastasis in gastric or colon cancer. This review summarizes the results about the role of IL-4/IL-13 and their receptors in gastric and colon cancer.

EHD2 Overexpression Suppresses the Proliferation, Migration, and Invasion in Human Colon Cancer

Background: To investigate how EHD2 influences the development of colon cancer. Methods: Immunohistochemistry of 90 colon cancer tissue specimens were determined the expression of EHD2. The lentivirus-EHD2-transfected colon cancer cells were conducted to evaluate the biological behaviors. Results: EHD2 was closely associated with clinic pathological parameters (p < 0.001). EHD2 upregulation was relative with a longer overall survival. The results of the univariate and multivariate analyses indicated that EHD2 could be an independent prognosis marker. EHD2 overexpression suppressed cell invasion and proliferation, but enhanced cell apoptosis and cell cycle arrest. Conclusions: EHD2 might represent a therapeutic target of colon cancer. IMPACT STATEMENT What is already known on this subject? Membrane trafficking is crucial for cell proliferation, differentiation and apoptosis, especially tumorigenesis and development. EHD2 proteins play an important role in the regulation of membrane trafficking in endocytosis. EHD2 has been suggested to participate in the occurrence of some malignancies. What are the new findings? EHD2 could be an independent prognosis marker in colon cancer. EHD2 overexpression suppressed cell invasion and proliferation, but enhanced cell apoptosis and cell cycle arrest in vitro. EHD2 overexpression markedly increased the expression of EMT marker E-cadherin in colon cancer. How might it impact on clinical practice in the foreseeable future? EHD2 overexpression may inhibit tumorigenesis in colon cancer through the modulation of E-cadherin, the critical marker of EMT which is closely related to invasion and distant metastasis of tumor cells.