scholarly journals miR-378a-5p inhibits the proliferation of colorectal cancer cells by downregulating CDK1

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kai Li ◽  
Jieling Zhang ◽  
Mingkang Zhang ◽  
Yaohua Wu ◽  
Xinyu Lu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Target Gene ◽  
Cell Function ◽  
Luciferase Reporter ◽  
Colorectal Cancer Cells ◽  
Pathological Tissues

Abstract Background MicroRNAs (miRNAs) play an important role in tumor occurrence. The role of miR-378a-5p and CDK1 in colorectal cancer (CRC) was investigated in this study. Methods Investigation of TCGA database and the detection of miR-378a-5p expression in colorectal cancer pathological tissues and colorectal cancer cell lines were undertaken by using qRT-PCR. We performed cell function experiments (CCK-8 assay, EdU assay, colony formation assay, wound healing assay, transwell assay, cell apoptosis assessment, and cell cycle assessment) and nude mouse tumor formation experiments to evaluate the effects of miR-378a-5p on proliferation, metastasis, and invasion to explore the role of miR-378a-5p in vivo and in vitro. Next, through TCGA database, immunohistochemical staining of pathological tissues, and cell function experiments, the role of the target gene CDK1 of miR-378a-5p was verified by database prediction, and dual luciferase reporter gene experiments in colorectal cancer cells were performed. Finally, whether upregulation of CDK1 restores the inhibitory effect of overexpression of miR-378a-5p on the proliferation of CRC cells was studied by overexpression of CDK1. Results Bioinformatic analysis showed significant downregulation of miR-378a-5p levels in colorectal cancer (CRC). Cell function experiments and tumor xenograft mouse models confirmed the low expression of miR-378a-5p within CRC tissues, which indicated the tumor suppressive role of miR-378a-5p in CRC. To better explore the regulation of miR-378a-5p in CRC, we predicted and validated cell cycle-dependent protein kinase 1 (CDK1) as the miR-378a-5p target gene and observed that miR-378a-5p suppressed CRC cell proliferation by targeting CDK1. Conclusion The results of this study help to elucidate the mechanism by which miR-378a-5p can be used as a tumor marker to inhibit the growth of colorectal cancer and CDK1, which is related to the prognosis of colorectal cancer patients. MiR-378a-5p inhibits CRC cell proliferation by suppressing CDK1 expression, which may become a possible therapeutic target for treatment of CRC.

scholarly journals miR-378a-5p inhibits the proliferation of colorectal cancer cells by downregulating CDK1

2020 ◽  
Author(s):  
Kai Li ◽  
Jieling zhang ◽  
Mingkang Zhang ◽  
Yaohua Wu ◽  
xinyu Lu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Function ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Mouse Tumor ◽  
The Impact ◽  
Pathological Tissues

Abstract Background MicroRNAs (miRNAs) exerts a vital part in tumor occurrence.The role of miR-378a-5p and CDK1 in colorectal cancer (CRC) was investigated in this study. Methods The investigation of TCGA database and the detection of miR-378a-5p expression in colorectal cancer pathological tissues and colorectal cancer cell lines were performed by using qRT-PCR. We conducted cell function experiments (CCK-8, EDU, Colony formation assay, Wound healing assay, Transwell assay, Cell apoptosis detection, Cell cycle detection) and nude mouse tumor formation experiments to evaluate the effects of miR-378a-5p on proliferation, metastasis, The impact of invasion to explore the role of miR-378a-5p in vivo and in vitro. Then, through the TCGA database, immunohistochemistry of pathological tissues, and cell function experiments, the role of the target gene CDK1 of miR-378a-5p verified by database prediction and dual luciferase reporter gene experiments in colorectal cancer was explored. Finally, whether up-regulation of CDK1 restores the inhibitory effect of overexpression of miR-378a-5p on the proliferation of CRC cells is studied by overexpression of CDK1. Results Bioinformatics analysis showed significant downregulation of miR-378a-5p level within colorectal cancer (CRC). Cell function experiments and tumor xenograft mouse models confirmed the low expression of miR-378a-5p within CRC tissues, which indicated the tumor suppression role of miR-378a-5p within CRC. For better exploring the regulation of miR-378a-5p in CRC, we predicted and validated cell cycle-dependent protein kinase 1 (CDK1) to be the miR-378a-5p target geneand found that miR-378a-5p suppressed CRC cell proliferation by targeting CDK1. Conclusion To sum up, results in this work discover the mechanism of miR-378a-5p in retarding CRC cell proliferation through suppressing CDK1 expression, and it may become a possible therapeutic target to treat CRC.

scholarly journals MSH2 is required for cell proliferation, cell cycle control and cell invasiveness in colorectal cancer cells

2012 ◽  
Vol 57 (20) ◽  
pp. 2580-2585
Author(s):  
Kai Shen ◽  
YingJiang Ye ◽  
KeWei Jiang ◽  
Bin Liang ◽  
XiaoDong Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Cycle Control ◽  
Colorectal Cancer Cells ◽  
Cell Invasiveness

scholarly journals Assessment of TRPV4 Channel and Its Role in Colorectal Cancer Cells

2019 ◽  
Vol 12 (2) ◽  
pp. 629-638
Author(s):  
N. N. Bahari ◽  
S. Y. N. Jamaludin ◽  
A. H. Jahidin ◽  
M. N. Zahary ◽  
A. B. Mohd Hilmi
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Cancer Cells ◽  
Human Colorectal Cancer ◽  
Expression Levels ◽  
Pharmacological Modulation ◽  
Colorectal Cancer Cells ◽  
Ht 29

The transient receptor potential vanilloid member 4 (TRPV4) is a non-selective calcium (Ca2+)-permeable channel which is widely expressed in different types of tissues including the lungs, liver, kidneys and salivary gland. TRPV4 has been shown to serve as a cellular sensor where it is involved in processes such as osmoregulation, cell volume regulation and thermoregulation. Emerging evidence suggests that TRPV4 also plays important roles in several aspects of cancer progression. Despite the reported roles of TRPV4 in several forms of cancers, the role of TRPV4 in human colorectal cancer remains largely unexplored. In the present study, we sought to establish the potential role of TRPV4 in colorectal cancer by assessing TRPV4 expression levels and investigating whether TRPV4 pharmacological modulation may alter cell proliferation, cell cycle and cell death in colorectal cancer cells. Quantitative real-time PCR analysis revealed that TRPV4 mRNA levels were significantly lower in HT-29 cells than normal colon CCD-18Co cells. However, TRPV4 mRNA was absent in HCT-116 cells. Pharmacological activation of TRPV4 with GSK1016790A significantly enhanced the proliferation of HT-29 cells while TRPV4 inhibition using RN 1734 decreased their proliferation. Increased proliferation in GSK1016790A-treated HT-29 cells was attenuated by co-treatment with RN 1734. Pharmacological modulation of TRPV4 had no effect on the cell cycle progression but promoted cell death in HT-29 cells. Taken together, these findings suggest differential TRPV4 expression levels in human colorectal cancer cells and that pharmacological modulation of TRPV4 produces distinct effects on the proliferation and induces cell death in HT-29 cells.

scholarly journals circRNA-UBAP2 promotes the proliferation and inhibits apoptosis of ovarian cancer though miR-382-5p/PRPF8 axis

2020 ◽  
Author(s):  
Qin Xu ◽  
Bo Deng ◽  
Manlin Li ◽  
Yang Chen ◽  
Li Zhuan
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Target Gene ◽  
Circular Rnas ◽  
Ovarian Cancer Cells ◽  
Competing Endogenous Rnas ◽  
Cancer Tissues

Abstract Objective: circular RNAs (circRNAs) have been reported to be essential regulators of multiple malignant cancers. However, the functions of circRNAs in ovarian cancer need to be further explored. The aim of our study is to explore the role of circRNA-UBAP2 in ovarian cancer and its mechanism. Results: circRNA-UBAP2 was upregulated in ovarian cancer tissues and cell lines. Knockdown of circRNA-UBAP2 inhibited cell proliferation and promoted cell apoptosis, but circRNA-UBAP2 overexpressed got opposite results. In addition, circRNA-UBAP2 targeted miR-382-5p and downregulated its expression, PRPF8 was a target gene of miR-382-5p. Furthemore, circRNA-UBAP2/miR-382-5p/PRPF8 axis affected the proliferation, apoptosis and cell cycle of ovarian cancer through the mechanism of competing endogenous RNAs (ceRNA). Conclusion: circRNA-UBAP2 acted as a ceRNA to sponged miR-382-5p, increased the expression level of PRPF8, and prompted proliferation and inhibited apoptosis in ovarian cancer cells.

scholarly journals circRNA-UBAP2 promotes the proliferation and inhibits apoptosis of ovarian cancer though miR-382-5p/PRPF8 axis

2020 ◽  
Author(s):  
Qin Xu ◽  
Bo Deng ◽  
Manlin Li ◽  
Yang Chen ◽  
Li Zhuan
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Target Gene ◽  
Circular Rnas ◽  
Ovarian Cancer Cells ◽  
Competing Endogenous Rnas ◽  
Cancer Tissues

Abstract Objective: circular RNAs (circRNAs) have been reported to be essential regulators of multiple malignant cancers. However, the functions of circRNAs in ovarian cancer need to be further explored. The aim of our study is to explore the role of circRNA-UBAP2 in ovarian cancer and its mechanism. Results: circRNA-UBAP2 was upregulated in ovarian cancer tissues and cell lines. Knockdown of circRNA-UBAP2 inhibited cell proliferation and promoted cell apoptosis, but circRNA-UBAP2 overexpressed got opposite results. In addition, circRNA-UBAP2 targeted miR-382-5p and downregulated its expression, PRPF8 was a target gene of miR-382-5p. Furthemore, circRNA-UBAP2/miR-382-5p/PRPF8 axis affected the proliferation, apoptosis and cell cycle of ovarian cancer through the mechanism of competing endogenous RNAs (ceRNA). Conclusion: circRNA-UBAP2 acted as a ceRNA to sponged miR-382-5p, increased the expression level of PRPF8, and prompted proliferation and inhibited apoptosis in ovarian cancer cells.

scholarly journals Intracellular Porphyromonas gingivalis Promotes the Proliferation of Colorectal Cancer Cells via the MAPK/ERK Signaling Pathway

2020 ◽  
Vol 10 ◽  
Author(s):  
Wenxin Mu ◽  
Yiqun Jia ◽  
Xiaobing Chen ◽  
Haoyu Li ◽  
Zhi Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cancer Cell ◽  
Erk Signaling ◽  
Colorectal Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Colorectal Cancer Cells

Porphyromonas gingivalis (P. gingivalis) is a keystone pathogen in periodontitis. However, several clinical studies have revealed an enrichment of P. gingivalis in the stool samples and colorectal mucosa of colorectal cancer patients. Thus, the goal of this study was to determine whether P. gingivalis can promote colorectal cancer progression in vitro. We established an acute infection model (24 h, multiplicity of infection =100) of P. gingivalis invasion of colorectal cancer cells to study the alterations induced by P. gingivalis in the proliferation and cell cycle of colorectal cancer cells. We observed that P. gingivalis can adhere and invade host cells a few hours after infection. Once invaded, P. gingivalis significantly promoted colorectal cancer cell proliferation, and the percentage of S phase cells was increased in the cell cycle assay. However, KDP136, a gingipain-deficient mutant of P. gingivalis 33277, showed a decreased ability to promote colorectal cancer cell proliferation, indicating that gingipain is associated with colorectal cancer cell proliferation. Furthermore, we extracted RNA from colorectal cancer cells for high-throughput sequencing analysis and reconfirmed the results by quantitative polymerase chain reaction and western blot analyses. The results suggested that the MAPK/ERK signaling pathway is significantly activated by P. gingivalis, while these changes were not observed for KDP136. In conclusion, P. gingivalis can invade cells and promote the proliferation of colorectal cancer cells by activating the MAPK/ERK signaling pathway. Gingipain is an essential virulence factor in this interaction.

scholarly journals Diphthamide Biosynthesis 1 is a Novel Oncogene in Colorectal Cancer Cells and is Regulated by MiR-218-5p

2017 ◽  
Vol 44 (2) ◽  
pp. 505-514 ◽  
Author(s):  
Minghui Liu ◽  
Kai Yin ◽  
Xu Guo ◽  
Huijin Feng ◽  
Min Yuan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Bioinformatics Analysis ◽  
Inverse Correlation ◽  
Luciferase Reporter ◽  
Pcr Analysis ◽  
Rt Pcr ◽  
Colorectal Cancer Cells ◽  
Invasion Assays

Background/Aims: This study focused on the oncogenic role of Diphthamide biosynthesis 1 (DPH1) in colorectal cancer (CRC) cells. Methods: The expression of DPH1 was determined by quantitative RT-PCR analysis and western blotting in CRC tissues. The role of DPH1 in CRC cells was investigated via cell viability and invasion assays under the condition of DPH1 silencing or overexpression. Bioinformatics analysis and luciferase reporter analysis were used to identify the upstream microRNA which might regulate DPH1.The inverse correlation between the microRNA and DPH1 was also detected in CRC cells. Results: We identified an unexpected role for DPH1 as an oncogene in CRC cells. The tumour-suppressive miR-218-5p regulates DPH1 directly and negatively. Loss of miR-218-5p drives the oncogenic role of DPH1 in CRC cells. Conclusion: The modulation of DPH1 by miR-218-5p may be an important regulatory axis during CRCtumourigenesis.

scholarly journals Rapid Loss of Intestinal Crypts upon Conditional Deletion of the Wnt/Tcf-4 Target Gene c-Myc

2006 ◽  
Vol 26 (22) ◽  
pp. 8418-8426 ◽  
Author(s):  
Vanesa Muncan ◽  
Owen J. Sansom ◽  
Leon Tertoolen ◽  
Toby J. Phesse ◽  
Harry Begthel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Target Gene ◽  
Gene Deletion ◽  
Physiological Role ◽  
Molecular Characteristics ◽  
Conditional Deletion ◽  
Colorectal Cancer Cells ◽  
Colorectal Cancer Cell Lines

ABSTRACT Inhibition of the mutationally activated Wnt cascade in colorectal cancer cell lines induces a rapid G1 arrest and subsequent differentiation. This arrest can be overcome by maintaining expression of a single Tcf4 target gene, the proto-oncogene c-Myc. Since colorectal cancer cells share many molecular characteristics with proliferative crypt progenitors, we have assessed the physiological role of c-Myc in adult crypts by conditional gene deletion. c-Myc-deficient crypts are lost within weeks and replaced by c-Myc-proficient crypts through a fission process of crypts that have escaped gene deletion. Although c-Myc − / − crypt cells remain in the cell cycle, they are on average much smaller than wild-type cells, cycle slower, and divide at a smaller cell size. c-Myc appears essential for crypt progenitor cells to provide the necessary biosynthetic capacity to successfully progress through the cell cycle.

scholarly journals Matrix degradation and cell proliferation are coupled to promote invasion and escape from an engineered human breast microtumor

2021 ◽  
Vol 13 (1) ◽  
pp. 17-29
Author(s):  
Emann M Rabie ◽  
Sherry X Zhang ◽  
Andreas P Kourouklis ◽  
A Nihan Kilinc ◽  
Allison K Simi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Type I ◽  
Matrix Degradation ◽  
Human Breast ◽  
Rate Of Invasion

Abstract Metastasis, the leading cause of mortality in cancer patients, depends upon the ability of cancer cells to invade into the extracellular matrix that surrounds the primary tumor and to escape into the vasculature. To investigate the features of the microenvironment that regulate invasion and escape, we generated solid microtumors of MDA-MB-231 human breast carcinoma cells within gels of type I collagen. The microtumors were formed at defined distances adjacent to an empty cavity, which served as an artificial vessel into which the constituent tumor cells could escape. To define the relative contributions of matrix degradation and cell proliferation on invasion and escape, we used pharmacological approaches to block the activity of matrix metalloproteinases (MMPs) or to arrest the cell cycle. We found that blocking MMP activity prevents both invasion and escape of the breast cancer cells. Surprisingly, blocking proliferation increases the rate of invasion but has no effect on that of escape. We found that arresting the cell cycle increases the expression of MMPs, consistent with the increased rate of invasion. To gain additional insight into the role of cell proliferation in the invasion process, we generated microtumors from cells that express the fluorescent ubiquitination-based cell cycle indicator. We found that the cells that initiate invasions are preferentially quiescent, whereas cell proliferation is associated with the extension of invasions. These data suggest that matrix degradation and cell proliferation are coupled during the invasion and escape of human breast cancer cells and highlight the critical role of matrix proteolysis in governing tumor phenotype.

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