scholarly journals Honeysuckle-derived microRNA2911 inhibits tumor growth by targeting TGF-β1

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Chunyan Liu ◽  
Mengzhen Xu ◽  
Luocheng Yan ◽  
Yulian Wang ◽  
Zhen Zhou ◽  
...  
Keyword(s):  
Colon Cancer ◽  
T Lymphocytes ◽  
High Stability ◽  
Tumor Tissue ◽  
Physiological Role ◽  
Original System ◽  
Luciferase Assay ◽  
Promoting Effect ◽  
Tgf Β1

Abstract Background Honeysuckle is a time‐honored herb with anticancer activity in traditional Chinese medicine. Recently, accumulating reports are suggesting that the microRNAs in this medicinal plant not only play a physiological role in their original system, but also can be transmitted to another species as potential therapeutic components. In the numerous bioactive investigations, the anti-tumor effects of these microRNAs in the magical herb are rarely studied, especially the special miR2911, a honeysuckle-encoded atypical microRNA, with high stability during the boiling process and unique biological activity to target TGF-β1 mRNA. Methods Luciferase assay was conducted to test the ability of miR2911 to target TGF-β1 mRNA. ELISA was performed to determine the expression level of TGF-β1 of mouse colorectal adenocarcinoma CT26 cells when treated with miR2911 and tumor tissue in Sidt1+/+ and Sidt1−/− mice. qRT-PCR was performed to examine the level of expression of miR2911. Tumor-bearing wild and nude mice were employed to evaluate the anti-tumor effect of honeysuckle and miR2911 in vivo. Tumor tissue necrosis was observed by H&E staining. Besides, the infiltration of T lymphocytes across solid tumors was tested by immunostaining staining. Results Our results showed that honeysuckle slowed the development of colon cancer down. Further research showed that miR2911 could bind strongly to TGF-β1 mRNA and down-regulate the expression of TGF-β1 and had a high stability under boiling and acid condition. Moreover, SIDT1 mediated dietary miR2911 inter-species absorption. And we found that miR2911 had a similar anticancer effect as honeysuckle. Mechanistically, miR2911 reversed the tumor-promoting effect of TGF-β1 by an increase of T lymphocytes infiltration, resulting in slowing the colon cancer process in immunocompetent mice. Consistent with this inference, the anti-tumor effect of miR2911 was revealed to be abolished in T cell immune deficiency mice. Conclusion Taken together, honeysuckle-derived miR2911 showed an anti-tumor effect in colon cancer through targeting TGF-β1 mRNA. The down-regulation of TGF-β1 promoted T lymphocytes infiltration, and accordingly impeded the colon tumor development.

scholarly journals Honeysuckle-Derived MicroRNA2911 Inhibits Tumor Growth by Targeting TGF-β1

2021 ◽  
Author(s):  
Chunyan Liu ◽  
Mengzhen Xu ◽  
Luocheng Yan ◽  
Yulian Wang ◽  
Zhen Zhou ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
High Stability ◽  
Tumor Tissue ◽  
Physiological Role ◽  
Original System ◽  
Luciferase Assay ◽  
Promoting Effect ◽  
Colon Cancers ◽  
Tgf Β1

Abstract Background: Honeysuckle is a time‐honored herb with anticancer activity in traditional Chinese medicine. Recently, accumulating reports are suggesting that the microRNAs in this medicinal plant not only play a physiological role in its original system, but also can be transmitted to another species as potential therapeutic components. In the numerous bioactive investigations, the anti-tumor effects of these microRNAs in the magical herb are rarely studied, especially the special miR2911, a honeysuckle-encoded atypical microRNA, with high stability during the boiling process and unique biological activity to target TGF-β1 mRNA. Methods: Luciferase assay was conducted to test the ability of miR2911 to target TGF-β1 mRNA. ELISA was performed to determine the expression level of TGF-β1 of mouse colorectal adenocarcinoma cells CT26 when treated with miR2911 and tumor tissue in Sidt1 +/+ and Sidt1 -/- mice. qRT-PCR was performed to examine the level of expression of miR2911. Tumor-bearing wild and nude mice were employed to evaluate the anti-tumor effect of honeysuckle and miR2911 in vivo . Tumor tissue necrosis was observed by H&E staining. Besides, the infiltration of T lymphocytes across solid tumors was tested by immunostaining staining. Results: Our results showed that honeysuckle slowed the development of colon cancers down. Further research showed that miR2911 could bind strongly to TGF-β1 mRNA and down-regulated the expression of TGF-β1 and had a high stability under boiling and acid condition. Moreover, SIDT1 mediated dietary miR2911 inter-species absorption. And we found that miR2911 had a similar anticancer effect as honeysuckle. Mechanistically, miR2911 reversed the tumor-promoting effect of TGF-β1 by an increase of T lymphocytes infiltration, resulting in slowing the colon cancer process in immunocompetent mice. Consistent with this inference, the anti-tumor effect of miR2911 was revealed to be abolished in T cell immune deficiency mice. Conclusion: Taken together, honeysuckle-derived miR2911 showed an anti-tumor effect in colon cancers though targeting TGF-β1 mRNA. The down-regulation of TGF-β1 promoted T lymphocytes infiltration, and accordingly impeded the colon tumor development.

scholarly journals Exosomal lncRNA PVT1/VEGFA Axis Promotes Colon Cancer Metastasis and Stemness by Downregulation of Tumor Suppressor miR-152-3p

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Shiue-Wei Lai ◽  
Ming-Yao Chen ◽  
Oluwaseun Adebayo Bamodu ◽  
Ming-Shou Hsieh ◽  
Ting-Yi Huang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Growth Factor ◽  
Cell Lines ◽  
Distant Metastasis ◽  
Cancer Metastasis ◽  
Lovo Cell ◽  
Promoting Effect ◽  
Colon Cancer Metastasis

Background. Treating advanced colon cancer remains challenging in clinical settings because of the development of drug resistance and distant metastasis. Mechanisms underlying the metastasis of colon cancer are complex and unclear. Methods. Computational analysis was performed to determine genes associated with the exosomal long noncoding (lncRNA) plasmacytoma variant translocation 1 (PVT1)/vascular endothelial growth factor A (VEGFA) axis in patients with colon cancer. The biological importance of the exosomal lncRNA PVT1/VEGFA axis was examined in vitro by using HCT116 and LoVo cell lines and in vivo by using a patient-derived xenograft (PDX) mouse model through knockdown (by silencing of PVT1) and overexpression (by adding serum exosomes isolated from patients with distant metastasis (M-exo)). Results. The in silico analysis demonstrated that PVT1 overexpression was associated with poor prognosis and increased expression of metastatic markers such as VEGFA and epidermal growth factor receptor (EGFR). This finding was further validated in a small cohort of patients with colon cancer in whom increased PVT1 expression was correlated with colon cancer incidence, disease recurrence, and distant metastasis. M-exo were enriched with PVT1 and VEGFA, and both migratory and invasive abilities of colon cancer cell lines increased when they were cocultured with M-exo. The metastasis-promoting effect was accompanied by increased expression of Twist1, vimentin, and MMP2. M-exo promoted metastasis in PDX mice. In vitro silencing of PVT1 reduced colon tumorigenic properties including migratory, invasive, colony forming, and tumorsphere generation abilities. Further analysis revealed that PVT1, VEGFA, and EGFR interact with and are regulated by miR-152-3p. Increased miR-152-3p expression reduced tumorigenesis, where increased tumorigenesis was observed when miR-152-3p expression was downregulated. Conclusion. Exosomal PVT1 promotes colon cancer metastasis through its association with EGFR and VEGFA expression. miR-152-3p targets both PVT1 and VEGFA, and this regulatory pathway can be explored for drug development and as a prognostic biomarker.

scholarly journals Exosomal lncRNA PVT1/VEGFA Axis Promotes Colon Cancer Metastasis and Stemness by Downregulation of Tumor Suppressor miR-152-3p

2020 ◽  
Author(s):  
Shiue-Wei Lai ◽  
Ming-Yao Chen ◽  
Ming-Shou Hsieh ◽  
Ting-Yi Huang ◽  
Chi-Tai Yeh ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Growth Factor ◽  
Cell Lines ◽  
Distant Metastasis ◽  
Colony Formation ◽  
Cancer Metastasis ◽  
Lovo Cell ◽  
Promoting Effect

Abstract Background: Late-stage colon cancer remains a treatment challenge in clinical settings because of the development of drug resistance and distant metastasis. Nevertheless, the mechanisms through which colon cancer cells acquire the ability to metastasize are complicated and require more research.Methods: Bioinformatic analysis was performed to determine gene associated with exosomal lncRNA PVT1/VEGFA axis of colon cancer patients. Biological importance of exosomal lncRNA PVT1/VEGFA axis was investigated in vitro (HCT116 and LoVo cell lines) and in vivo (PDX mouse model) through knockdown (siPVT1) and overexpression (add exosomes from sera of distant metastasis patients). PVT1/VEGFA axis related protein expression in and cell lines were investigated through RT-qPCR, immunoblotting, and immunohistochemistry analysis. Colony formation Assay, cell invasion, migration, and tumorsphere-formation assay were used to explore possible molecular mechanism. Results: First, using public databases, we demonstrated that PVT1 overexpression is associated with poor prognosis and increased metastatic markers, such as vascular endothelial growth factor A (VEGFA) and epidermal growth factor receptor (EGFR). This finding was then validated in a small cohort of patients with colon cancer, where increased PVT1 expression was correlated with colon cancer incidence, disease recurrence, and distant metastasis. Notably, serum exosomes from patients with metastatic (M-exo) colon cancer were enriched with PVT1 and VEGFA and increased both migratory and invasive abilities in colon cancer cell lines when cocultured. This metastasis-promoting effect was accompanied by an increased expression of Twist1, Vimentin, and MMP2. Notably, M-exo promoted metastatic incidence in patient-derived xenograft mice. In vitro silencing of PVT1 led to decreased colon tumorigenic properties, including colony formation, tumorsphere formation, and metastatic potential. Further analysis revealed that miR-152-3p has multiple targets, including PVT1, VEGFA, and EGFR. Increased miR-152-3p resulted in decreased tumorigenesis, and the reverse was true when the miR-152-3p level was decreased.Conclusion: In conclusion, we provided evidence regarding the role of exosomal PVT1 in promoting metastasis in colon cancer through its association with EGFR and VEGFA expression. PVT1 and VEGFA are both targets of miR-152-3p, and this regulatory pathway could be explored for drug and prognostic biomarker development.

scholarly journals miR-181a-2-3p Stimulates Gastric Cancer Progression via Targeting MYLK

2021 ◽  
Vol 9 ◽  
Author(s):  
Jianjie Li ◽  
Xiaoyue Xu ◽  
Chunhui Liu ◽  
Xiaoxue Xi ◽  
Yang Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Myosin Light Chain ◽  
Cell Counting ◽  
Luciferase Assay ◽  
Promoting Effect ◽  
Cell Progression ◽  
Gastric Cancer Progression

Background: The abnormal expression of miRNAs facilitates tumorigenesis and development. miR-181a-2-3p is up-regulated in various cancers, yet its mechanism in gastric cancer (GC) remains elusive.Objective: To understand mechanism of miR-181a-2-3p stimulating GC cell progression via targeting Myosin Light Chain Kinase (MYLK) expression.Methods: Downstream genes of miRNA of interest were predicted in TargetScan and miRTarBase. qRT-PCR and western blot were applied to assess miR-181a-2-3p and MYLK expression in GC cells and normal cells. Dual-luciferase and RIP assays were completed to assess binding of miR-181a-2-3p and MYLK. Cell Counting Kit-8 (CCK-8) assay was conducted for detecting viability of AGS and SNU-1 cells, while Transwell tested migratory and invasive abilities of cells. Nude mouse transplantation tumor experiment was performed to assay tumor growth in vivo.Results: miR-181a-2-3p was notably increased in human GC cell lines, while MYLK was remarkably down-regulated. RIP and dual-luciferase assay disclosed that miR-181a-2-3p targeted MYLK and repressed MYLK. Forced miR-181a-2-3p expression fostered GC cell proliferation, invasion, migration, and fostered tumor growth in vivo. Promoting effect of miR-181a-2-3p on GC cells was reversed when miR-181a-2-3p and MYLK were simultaneously overexpressed.Conclusion: miR-181a-2-3p facilitated GC cell progression by targeting MYLK, and it may be a pivotal prognostic biomarker in investigating molecular mechanism of GC.

scholarly journals Mir-124 Attenuates STAT3-Mediated TH17 Differentiation in Colitis-Driven Colon Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Shiyong Lin ◽  
Qianwen Liu ◽  
Jing Wen ◽  
Kunhao Bai ◽  
Yandong Guo ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Polarization ◽  
Luciferase Assay ◽  
Transfer Model ◽  
Mice Model ◽  
Colon Tumorigenesis ◽  
Th17 Differentiation ◽  
T Cell Transfer

BackgroundInflammation often induces regeneration to repair the tissue damage. However, chronic inflammation can transform temporary hyperplasia into a fertile ground for tumorigenesis. Here, we demonstrate that the miR-124 acts as a safeguard to inhibit the pro-inflammatory production and reparative regeneration.MethodsThe expression levels of miR-124 and IL-17, IFN-γ were detected by qRT-PCR. TH17 or TH1 cells were detected by flow cytometer, respectively. The binding of STAT3 to the promoter region of IL-17 gene was analyzed by Chip assay. miR-124 binding to the 3′UTR of STAT3 gene was detected by reported plasmid construction and luciferase assay. Furthermore, DSS-induced colitis mice model and T cell transfer model were used to confirm the function of miR-124 in vivo. The related gene expression was analyzed by ELISA and western blot experiments.ResultsThe results indicated that miR-124 decrease promotes colon tumorigenesis after Citrobacter rodentium infection and AOM/DSS induced colon cancer murine model. In molecular mechanism, miR-124 targets STAT3 to inhibit TH17 cell polarization and keep TH17 polarization in colonic microenvironment.ConclusionsOur study strengthened the important role of miR-124 in the regulation of adaptive immune responses and blocking the development of colitis-related cancer.

scholarly journals MiR-27b-3p inhibits the progression of renal fibrosis via suppressing STAT1

Human Cell ◽  
2021 ◽  
Vol 34 (2) ◽  
pp. 383-393
Author(s):  
Lin Bai ◽  
Yongtao Lin ◽  
Juan Xie ◽  
Yiyuan Zhang ◽  
Hongwu Wang ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Luciferase Assay ◽  
Mesenchymal Transition ◽  
Collagen Iii ◽  
Tgf Β1 ◽  
Active Caspase

AbstractRenal fibrosis is a pathologic change in chronic kidney disease (CKD). MicroRNAs (miRNAs) have been shown to play an important role in the development of renal fibrosis. However, the biological role of miR-27b-3p in renal fibrosis remains unclear. Thus, this study aimed to investigate the role of miR-27b-3p in the progression of renal fibrosis. In this study, HK-2 cells were stimulated with transforming growth factor (TGF)-β1 for mimicking fibrosis progression in vitro. The unilateral ureteric obstruction (UUO)-induced mice renal fibrosis in vivo was established as well. The results indicated that the overexpression of miR-27b-3p significantly inhibited epithelial-to-mesenchymal transition (EMT) in TGF-β1-stimulated HK-2 cells, as shown by the decreased expressions of α-SMA, collagen III, Fibronectin and Vimentin. In addition, overexpression of miR-27b-3p markedly decreased TGF-β1-induced apoptosis in HK-2 cells, as evidenced by the decreased levels of Fas, active caspase 8 and active caspase 3. Meanwhile, dual-luciferase assay showed that miR-27b-3p downregulated signal transducers and activators of transcription 1 (STAT1) expression through direct binding with the 3′-UTR of STAT1. Furthermore, overexpression of miR-27b-3p attenuated UUO-induced renal fibrosis via downregulation of STAT1, α-SMA and collagen III. In conclusion, miR-27b-3p overexpression could alleviate renal fibrosis via suppressing STAT1 in vivo and in vitro. Therefore, miR-27b-3p might be a promising therapeutic target for the treatment of renal fibrosis.

Preoperative Mobilization of Circulating Dendritic Cells by Flt3 Ligand Administration to Patients With Metastatic Colon Cancer

2000 ◽  
Vol 18 (23) ◽  
pp. 3883-3893 ◽  
Author(s):  
Michael A. Morse ◽  
Smita Nair ◽  
Monica Fernandez-Casal ◽  
Yuping Deng ◽  
Michelle St Peter ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Peripheral Blood ◽  
Tumor Tissue ◽  
Mononuclear Cells ◽  
Metastatic Tumor ◽  
Delayed Type Hypersensitivity ◽  
Metastatic Colon Cancer ◽  
Flt3 Ligand ◽  
Peripheral Blood Mononuclear

PURPOSE: To evaluate preoperative dendritic cell (DC) mobilization and tumor infiltration after administration of Flt3 ligand (Flt3L) to patients with metastatic colon cancer. PATIENTS AND METHODS: Twelve patients with colon cancer metastatic to the liver or lung received Flt3L (20 μg/kg/d subcutaneously for 14 days for one to three cycles at monthly intervals) before attempted metastasectomy. The number and phenotype of DCs mobilized into peripheral-blood mononuclear cells (PBMCs) were evaluated by flow cytometry. After surgical resection, metastatic tumor tissue was evaluated for DC infiltration. In vivo immune responses to recall antigens were measured. RESULTS: After Flt3L administration, on average, the total number of leukocytes in the peripheral blood increased from 5.9 ± 1.0 × 103/mm3 to 11.2 ± 3.8 × 103/mm3 (mean ± SD, P = .0001). The percentage of CD11c+CD14− DCs in PBMCs increased from 2.4% ± 1.8% to 8.8% ± 4.7% (P = .004). Delayed-type hypersensitivity (DTH) responses to recall antigens (Candida, mumps, and tetanus) showed marginally significant increases in reactivity after Flt3L administration (P = .06, P = .03, and P = .08, respectively). An increase in the number of DCs was observed at the periphery of the tumors of patients who received Flt3L compared with those of patients who had not. CONCLUSION: Flt3L is capable of mobilizing DCs into the peripheral blood of patients with metastatic colon cancer and may be associated with increases in DC infiltration in the peritumoral regions. Flt3L mobilization is associated with a trend toward increased DTH responses to recall antigens in vivo. The use of Flt3L to increase circulating DCs for cancer immunotherapy should be considered.

In vivo localization of a bispecific antibody which targets human t lymphocytes to lyse human colon cancer cells

1989 ◽  
Vol 43 (3) ◽  
pp. 501-507 ◽  
Author(s):  
Ian G. Barr ◽  
Sylvia Miescher ◽  
Vladimir Von Fliedner ◽  
Franz Buchegger ◽  
Catherine Barras ◽  
...  
Keyword(s):  
Colon Cancer ◽  
T Lymphocytes ◽  
Cancer Cells ◽  
Bispecific Antibody ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Human T Lymphocytes ◽  
Human Colon Cancer Cells

Tumor Localization and Quantitation of Adoptively Transfered T Lymphocytes in a Murine Model.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1343-1343
Author(s):  
Marianne Hokland ◽  
Mikkel S. Petersen ◽  
Charlotte C. Fleischer ◽  
Hans Stødkilde-Jørgensen ◽  
Søren B. Hansen ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
T Lymphocytes ◽  
Cd8 T Cells ◽  
Tumor Tissue ◽  
Cellular Therapy ◽  
Mean Value ◽  
Tumor Localization ◽  
Toxic Substances

Abstract Tracking adoptively transferred antigen-specific T lymphocytes is an important prerequisite for devising better protocols for cellular therapy. To this end we have developed a highly sensitive method for “in situ” visualization of labelled lymphocytes in vivo by combined PET and magnetic resonance imaging (MRI) to monitor the distribution of adoptively transferred tumour-specific T cells in a mouse model system. Moreover, quantitation of the adoptively transferred cells in tumor was performed by flow cytometry. C57BL/6J mice carrying subcutaneous tumours of the ovalbumin (OVA)-expressing malignant melanoma cell line B16-OVA were adoptively transferred with OVA-specific CD8+ T cells labelled with 124IdU. Five days after transfer of T cells, mice were killed and subjected to PET and MR imaging. Using a newly developed method for co-registration of the two image modalities, the anatomical localisation of the transferred cells was visualised and the amount of radioactivity in various anatomical locations very accurately determined. For quantitation of tumor infiltrating non-labelled OVA-specific CD8+ T cells by flow cytometry (using AbsoluteCount Beads), tumors were removed from mice day 1 until day 8 following adoptive transfer (6 mice/group) and prepared for single cell suspension before labeled with anti-CD8-FITC and SIINFEKL-Tetramer-PE. Results showed a clear tumor localization of the adoptively transferred OVA-specific T cells in the tumours. In two independent experiments comprising 12 and 13 evaluable mice, respectively, we found a mean value of 0.909 +/− 0.468 Bq and 0.926 +/− 0.553 Bq in the tumours, and only 0.182 +/− 0.479 Bq and 0.026 +/− 0.480 Bq in the corresponding contralateral control volumes. The difference in activity between the tumour regions and the control regions was statistically highly significant with 2p-values of 0.002 and 0.006 for the two experiments. Using flow cytometry it was shown that the number of OVA specific T lymphocytes accumulating in tumor gradually increased until day 5 after transfer when an average of 3.3 million SIINFEKL-specific cells per gram tumor tissue was found. From day 5 until day 8 the number of SIINFEKL-specific cells per gram tumor tissue fluctuated at a fairly constant level. This method presented for tracking adoptively transfered tumor specific T lymphocytes represent a significant advancement for studies of adoptively transferred specific T cells, and could potentially be developed for diagnostic purposes. Moreover, since these studies show that tumor-specific T cells home to subcutaneous tumours in substantial numbers, we suggest that these migrating cells could be employed in a new form of therapy as carriers of toxic substances to tumors.

scholarly journals Effect of rs67085638 in long non-coding RNA (CCAT1) on colon cancer chemoresistance to paclitaxel through modulating the microRNA-24-3p and FSCN1 signaling

2020 ◽  
Author(s):  
Caihong Zhang ◽  
Yonglin Wang
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Luciferase Assay ◽  
Pcr Analysis ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Protein Levels ◽  
The Difference

Abstract BackgroundIt has been reported that rs67085638 in lncRNA-CCAT1 was associated with the risk of tumorigenesis. Also, CCAT1 could affect chemoresistance of cancer cells to PTX via regulating miR-24-3p and FSCN1 expression. In this study, we aimed to investigate the effect of rs67085638 on the expression of CCAT1/miR-24-3p/FSCN1 and the response of colon cancer to the treatment of PTX.Method48 colon cancer patients were recruited and grouped by their genotypes of rs67085638 polymorphism as a CC group (N=28) and a CT group (N=20). Colon cancer cells were collected from the patients and cancer cell xenografts were transplanted into mice. PCR analysis, IHC assay and Western blot were performed to observe the expression of lncRNA-CCAT1, miR-24-3p and FSCN1 in vivo and in vitro, and the relationships among the expression of lncRNA-CCAT1, miR-24-3p and FSCN1 were validated by computational analysis and luciferase assay. TUNEL assay and flow cytometry were conducted to observe tumor cell apoptosis and survival.ResultLncRNA-CCAT1 and FSCN1 mRNA/protein were over-expressed while miR-24-3p was down-regulated in the CT-genotyped patients and cells compared with those in the CC-genotyped patients and cells. The survival of colon cancer cells was decreased while the apoptosis of colon cancer cells was increased by PTX treatment in a dose-dependent manner. However, the survival rate of CT-genotyped cells was higher while the apoptosis rate of CT-genotyped cells was lower than that of the CC-genotyped cells, and the difference was partly eliminated by the knockdown of lncRNA-CCAT1. MiR-24-3p was validated to target lncRNA-CCAT1 and FSCN1 mRNA, and the over-expression of CCAT1 could reduce the expression of miR-24-3p while elevating the expression of FSCN1. The growth of CT-genotyped tumors in mice was more suppressed in compared with the growth of CC-genotyped tumors, while the knockdown of lncRNA-CCAT1 partly reversed the effect of the CT genotype. Furthermore, compared with the rs67085638-CC mice, the lncRNA-CCAT1 and FSCN1 mRNA/protein levels in the rs67085638-CT+NC shRNA mice were increased while their miR-24-3p level was decreased, and the knockdown of lncRNA-CCAT1 partly reversed the dysregulation of these genes.ConclusionThe findings of this study demonstrated that the presence of the minor allele of rs67085638 increased the expression of CCAT1 and accordingly enhanced the resistance to PTX. Downregulation of CCAT1 partially, but significantly, re-stored the sensitivity to PTX of colon cancer cells.

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