SNORA71A Promotes Colorectal Cancer Cell Proliferation, Migration, and Invasion

Small nucleolar RNAs (snoRNAs) play a crucial role during colorectal cancer (CRC) development. The study of SNORA71A is few, and its role in CRC is unknown. This study focused on screening abnormal snoRNAs in CRC and exploring the role of key snoRNA in CRC. The expression pattern of snoRNAs in 3 CRC and 3 normal colon tissues was detected via small RNA sequencing. The six candidate snoRNAs were identified by quantitative PCR (qPCR). Subsequently, the expression level of SNORA71A was further verified through the Cancer Genome Atlas (TCGA) data analysis and qPCR. The CCK8 and transwell assays were used to detect the functional role of SNORA71A in CRC cells. The integrated analysis of snoRNA expression profile indicated that a total 107 snoRNAs were significantly differentially expressed (DE) in CRC tissues compared with normal tissues, including 45 upregulated and 62 downregulated snoRNAs. Bioinformatics analysis revealed that the DE snoRNAs were mainly implicated in “detection of chemical stimulus involved in sensory perception of smell” and “sensory perception of smell” in the biological process. The DE snoRNAs were preferentially enriched in “olfactory transduction” and “glycosphingolipid biosynthesis-ganglio series pathway.” The expression of SNORA71A was upregulated in CRC tissues and cells. SNORA71A expression showed statistically significant correlations with TNM stage ( P = 0.0196 ) and lymph node metastasis ( P = 0.0189 ) and can serve as biomarkers for CRC. Importantly, SNORA71A significantly facilitated the CRC cell proliferation, migration, and invasion. Our findings indicate that SNORA71A screened by sequencing acted as an oncogene and promoted proliferation, migration, and invasion ability of CRC cells.

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RACK1 Acts as a Potential Tumor Promoter in Colorectal Cancer

Gastroenterology Research and Practice ◽

10.1155/2019/5625026 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8

Author(s):

Xue-Yang Li ◽

Yi Hu ◽

Nian-Shuang Li ◽

Jian-Hua Wan ◽

Yin Zhu ◽

...

Keyword(s):

Colorectal Cancer ◽

The Cancer Genome Atlas ◽

Biological Role ◽

Tumor Promoter ◽

Migration And Invasion ◽

Loss Of Function ◽

Normal Tissues ◽

Geo Dataset

Background. The receptor of activated protein kinase C 1 (RACK1) promotes the progression and invasion of several cancers. However, the role of RACK1 in the pathogenesis of colorectal cancer (CRC) has not been clearly defined. Herein, we aimed to investigate the biological role of RACK1 in CRC. Materials and Methods. The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) dataset were searched, and the expression of RACK1 in CRC tissues and adjacent normal tissues was evaluated. Immunohistochemical staining was performed to detect the expression of RACK1 in human CRC, adenoma, and normal tissues. Western blotting was used to detect the expression of RACK1 in human CRC cell lines. Functional assays, such as BrdU, colony formation, and wound healing and transwell invasion assays, were used to explore the biological role of RACK1 in CRC. Results. RACK1 was upregulated in CRC tissues compared with its expression in adjacent normal tissues in TCGA and the GEO dataset (P<0.05). Moreover, RACK1 was significantly overexpressed in CRC and adenoma tissues compared with its expression in normal tissues (P<0.05). Loss-of-function experiments showed that RACK1 promoted cell proliferation, migration, and invasion in vitro. Conclusions. Our data indicated that RACK1, as an oncogene, markedly promoted the progression of CRC, which suggested that RACK1 is a potential therapeutic target for CRC management.

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miR-17-5p promotes the invasion and migration of colorectal cancer by regulating HSPB2

10.21203/rs.3.rs-63587/v2 ◽

2020 ◽

Author(s):

Wei fang Yu ◽

Jia Wang ◽

Chao Li ◽

Mingda Xuan ◽

Shuangshuang Han ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Lymph Node ◽

Target Genes ◽

Migration And Invasion ◽

Invasion And Migration ◽

Normal Tissues ◽

Node Metastasis ◽

Rescue Experiment ◽

And Migration

Abstract Background: MicroRNA (miRNA) can affect tumor progression by regulating cell proliferation, apoptosis and metastasis. After miRNA microarray chip analysis of colorectal cancer (CRC) tissues and adjacent normal tissues, a significant upregulation of miR-17-5p expression was found in CRC tissues. However, the underlying mechanism of miR-17-5p in CRC is still unclear.Methods: The levels of miR-17-5p in 47 paired CRC and adjacent normal tissue samples were determined by quantitative real-time PCR (qRT-PCR). CCK-8, colony formation, flow cytometry and transwell assays were used to explore the biological effects of miR-17-5p on CRC cells. In addition, the transcriptome sequencing and miRNA target prediction software were employed to identify targets of miR-17-5p. Luciferase reporter detection was used to demonstrate the direct binding of target genes by miR-17-5p. The rescue experiment was conducted to investigate the biological function of target genes and regulatory mechanism of miR-17-5p on target genes.Results: The expression of miR-17-5p was significantly higher in CRC tissues than in adjacent normal tissues. In CRC group, the expression of miR-17-5p in cancer tissues with lymph node metastasis was higher compared with those without lymph node metastasis. Overexpression of miR-17-5p inhibited CRC cell apoptosis, as well as promoting proliferation, migration and invasion. We hypothesized that HSPB2 might be a target gene of miR-17-5p and validated for the first time that miR-17-5p binds directly to the 3’-UTR of HSPB2. In the rescue experiment, the tumor suppressive effect of HSPB2 was detected and miR-17-5p could promote cell proliferation, migration and invasion by targeting HSPB2.Conclusion: MiR-17-5p promotes invasion and migration by inhibiting HSPB2 in CRC, thereby implicating its potential as a novel diagnostic biomarker and therapeutic target for CRC.

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Acyl-CoA Synthetase 5 Promotes the Growth and Invasion of Colorectal Cancer Cells

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2017/7615736 ◽

2017 ◽

Vol 2017 ◽

pp. 1-14 ◽

Cited By ~ 3

Author(s):

Shihua Ding ◽

Shaohui Tang ◽

Min Wang ◽

Donghai Wu ◽

Haijian Guo

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Cell Migration ◽

Cell Apoptosis ◽

Migration And Invasion ◽

Cell Migration And Invasion ◽

Sw620 Cells ◽

Role Of It

Background and Aims. Acyl-CoA synthetase 5 (ACS5) has been reported to be associated with the development of various cancers, but the role of it in colorectal cancer (CRC) is not well understood. The present study aimed to explore the potential role of ACS5 in the development and progression of CRC. Methods. ACS5 expression in CRC tissues and CRC cell lines was examined, and its clinical significance was analyzed. The role of ACS5 in cell proliferation, apoptosis, and invasion was examined in vitro. Results. We found that ACS5 expression was upregulated in CRC cells and CRC tissues and that high ACS5 expression was more frequent in CRC patients with excess muscular layer and with poor tumor differentiation. Furthermore, knockdown of ACS5 in HT29 and SW480 cells significantly dampened cell proliferation, induced cell apoptosis, and reduced cell migration and invasion. In contrast, the ectopic overexpression of ACS5 in LOVO and SW620 cells remarkably promoted cell proliferation, inhibited cell apoptosis, and enhanced cell migration and invasion. Enhanced cell growth and invasion ability mediated by the gain of ACS5 expression were associated with downregulation of caspase-3 and E-cadherin and upregulation of survivin and CD44. Conclusions. Our data demonstrate that ACS5 can promote the growth and invasion of CRC cells and provide a potential target for CRC gene therapy.

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Identification of circular RNA hsa_circ_0044556 and its effect on the progression of colorectal cancer

10.21203/rs.3.rs-26944/v2 ◽

2020 ◽

Author(s):

Liang Jing ◽

Junhui Wu ◽

Xiaocheng Tang ◽

Min Ma ◽

Fei Long ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Lines ◽

Tumor Stage ◽

Circular Rna ◽

Gene Expression Omnibus ◽

Migration And Invasion ◽

Circular Rnas ◽

Normal Tissues ◽

Node Metastasis

Abstract Background: Circular RNAs (circRNAs) are a novel class of noncoding RNAs. Increasing evidence indicates that circRNAs play an important role in the occurrence and development of tumors. However, the role of circRNA hsa_circ_0044556 in the progression of colorectal cancer (CRC) remains unclear. Methods: First, we searched for differentially expressed circRNAs using a circRNA microarray in paired CRC and adjacent normal tissues. The circRNA hsa_circ_0044556 was screened out from the existing CRC circRNA microarray in the Gene Expression Omnibus database and our microarray. The clinical significance of hsa_circ_0044556 expression level in CRC patients was then investigated. Finally, the functions of the targets of this circRNA were determined in CRC cell lines.Results:Hsa_circ_0044556 was highly expressed in CRC patients and was positively correlated with tumor stage and lymph node metastasis. In CRC cell lines, the proliferation, migration, and invasion of cancer cells were inhibited by knocking down hsa_circ_0044556 expression.Conclusion: Hsa_circ_0044556 promoted the progression of CRC. It is possible that hsa_circ_0044556 will become a novel biomarker or therapeutic target for CRC.

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Restoring HOXD10 Exhibits Therapeutic Potential for Ameliorating Malignant Progression and 5-Fluorouracil Resistance in Colorectal Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.771528 ◽

2021 ◽

Vol 11 ◽

Author(s):

Weijie Pan ◽

Kaijing Wang ◽

Jiayong Li ◽

Hanhua Li ◽

Yuchan Cai ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Lines ◽

Therapeutic Potential ◽

Methylation Status ◽

Suppressor Gene ◽

Resistant Cell ◽

The Cancer Genome Atlas ◽

Migration And Invasion ◽

Dependent Manner ◽

Normal Tissues

Emerging evidence suggests that hypermethylation of HOXD10 plays an important role in human cancers. However, the biological and clinical impacts of HOXD10 overmethylation and its downstream targets in colorectal cancer remain unknown. We evaluated the methylation level of HOXD10 in paired cancer and normal tissues (n = 42) by using pyrosequencing, followed by validation of the methylation status of HOXD10 from The Cancer Genome Atlas (TCGA) datasets with 302 cancer tissues and 38 normal tissues. The biological function of HOXD10 was characterized in cell lines. We further evaluated the effects of HOXD10 and its targets on chemoresistance in our established resistant cell lines and clinical cohort (n = 66). HOXD10 was found frequently methylated in colorectal cancer, and its hypermethylation correlates with its low expression level, advanced disease, and lymph node metastasis. Functionally, HOXD10 acts as a tumor suppressor gene, in which HOXD10-expressing cells showed suppressed cell proliferation, colony formation ability, and migration and invasion capacity. Mechanistically, DNMT1, DNMT3B, and MeCP2 were recruited in the HOXD10 promoter, and demethylation by 5-Aza-2′-deoxycytidine (5-Aza-CdR) treatment or MeCP2 knockdown can sufficiently induce HOXD10 expression. HOXD10 regulates the expressions of miR-7 and IGFBP3 in a promoter-dependent manner. Restoration of the expression of HOXD10 in 5-fluorouracil (5-FU)-resistant cells significantly upregulates the expressions of miR-7 and IGFBP3 and enhances chemosensitivity to 5-FU. In conclusion, we provide novel evidence that HOXD10 is frequently methylated, silenced, and contributes to the development of colorectal cancers. Restoration of HOXD10 activates the expressions of miR-7 and IGFBP3 and results in an inhibited phenotype biologically, suggesting its potential therapeutic relevance in colorectal cancer (CRC).

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miR-17-5p Promotes the Invasion and Migration of Colorectal Cancer by Regulating HSPB2

10.21203/rs.3.rs-63587/v1 ◽

2020 ◽

Author(s):

Wei fang Yu ◽

Jia Wang ◽

Chao Li ◽

Mingda Xuan ◽

Shuangshuang Han ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Lymph Node ◽

Target Genes ◽

Migration And Invasion ◽

Invasion And Migration ◽

Normal Tissues ◽

Node Metastasis ◽

Rescue Experiment ◽

And Migration

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miR-188-5p Suppresses Gastric Cancer Cell Proliferation and Invasion via Targeting ZFP91

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504018x15191223015016 ◽

2018 ◽

Vol 27 (1) ◽

pp. 65-71 ◽

Cited By ~ 24

Author(s):

Yuping Peng ◽

Xuning Shen ◽

Honggang Jiang ◽

Zhiheng Chen ◽

Jiaming Wu ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Inverse Correlation ◽

Migration And Invasion ◽

Normal Tissues ◽

Promising Therapeutic Target ◽

Cellular Apoptosis ◽

Gastric Cancer Cell Proliferation

MicroRNAs (miRNAs) have been demonstrated to be essential regulators in the development and progression of various cancers. The role of miR-188-5p in gastric cancer (GC) has not been determined. In this study, we found that the expression of miR-188-5p was downregulated in GC tissues compared with adjacent normal tissues. The lowly expressed miR-188-5p was significantly associated with lymph node metastasis and advanced TNM stage. Moreover, overexpression of miR-188-5p significantly inhibited GC cell proliferation, migration, and invasion but promoted cellular apoptosis. Mechanistically, we identified transcription factor ZFP91 as a target gene of miR-188-5p in GC. We found that miR-188-5p overexpression significantly inhibited the expression of ZFP91 in GC cell lines. There was an inverse correlation between the expression of miR-188-5p and ZFP91 in GC tissues. We found that restoration of ZFP91 in miR-188-5p-overexpressed MGC-803 and SGC-7901 cells promoted cell proliferation, migration, and invasion. Finally, we also showed that overexpression of miR-188-5p inhibited tumor growth in vivo. Taken together, our findings indicated that miR-188-5p serves as a tumor suppressor in human GC by targeting ZFP91, suggesting that miR-188-5p might be a promising therapeutic target for GC treatment.

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MiR-423-3p Enhances Cell Growth Through Inhibition of p21Cip1/Waf1 in Colorectal Cancer

Cellular Physiology and Biochemistry ◽

10.1159/000430230 ◽

2015 ◽

Vol 37 (3) ◽

pp. 1044-1054 ◽

Cited By ~ 18

Author(s):

Hong-tao Li ◽

Hui Zhang ◽

Yong Chen ◽

Xian-fu Liu ◽

Jun Qian

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Cell Growth ◽

Vital Role ◽

Luciferase Reporter ◽

Normal Tissues ◽

Non Coding Rnas ◽

And Migration

Background/Aims: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths globally, with many oncogenes and tumor suppressors involved. The miRNAs are small non-coding RNAs known to play a vital role in the pathogenesis of CRC. The miR-423-3p was reported to act as an oncogene; however, its role in CRC growth remains unknown. Methods: qPCR assay was used to detect miR-423-3p expression in CRC specimens. Cell proliferation assay and transwell assay were conducted to evaluate CRC cell proliferation and migration. Luciferase reporter assay was to identify the target gene of miR-423-3p. And tumorigenesis model was established to test the role of miR-423-3p in CRC development in vivo. Results: Here, we showed that miR-423-3p was significantly up regulated in CRC tissues and cells compared with normal tissues and cells. Overexpression of miR-423-3p promoted CRC cell proliferation via enhancing the G1/S transition phase of the cell cycle, while inhibition of miR-423-3p repressed cell growth. Further studies showed that p21Cip1/Waf1 mediated the function of miR-423-3p, and overexpression of p21Cip1/Waf1 reversed the augmented effect of miR-423-3p on cell proliferation. Importantly, all these data were validated in the tumorigenesis assay in vivo. Conclusions: In conclusion, our findings demonstrated a critical impact of miR-423-3p on CRC growth.

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MicroRNA-188-5p targeting Forkhead Box L1 promotes colorectal cancer progression via activating Wnt/β-catenin signaling

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504020x16061317886881 ◽

2020 ◽

Author(s):

Jialin Wu ◽

Zehong Chen ◽

Wenwei Liu ◽

Yongxin Zhang ◽

Wei Feng ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Wnt Signaling ◽

Cell Lines ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Beta Catenin ◽

Advanced Tumor Stage ◽

Normal Tissues ◽

Advanced Tumor

MicroRNA-188-5p (miR-188) enhances oncologic progression in various human malignancies. This study aimed to explore its role in colorectal cancer (CRC). Human CRC tissues paired with normal tissues, and several CRC cell lines were utilized. Real-time quantitative PCR was applied to measure the expression of miR-188. Overexpression and knockdown were used to access the function of miR-188 and to investigate whether FOXL1/Wnt signaling mediates such function. The proliferation, migration and invasion of cancer cells were evaluated by CCK8, wound-healing and transwell assays, respectively. Whether FOXL1 acted as a direct target of miR-188 was verified by dual-luciferase reporter assays. Levels of miR-188 were upregulated in CRC tissues than in paired-normal tissues, as well as in various CRC cell lines. High expression of miR-188 was strongly associated with advanced tumor stage, accompanied with significant tumor cell proliferation, invasion and migration. It was confirmed that FOXL1 played positive crosstalk between miR-188 regulation and downstream Wnt/β-catenin signaling activation. All findings indicate that miR-188 promotes CRC cell proliferation and invasion through targeting FOXL1/Wnt signaling and could be served as a potential therapeutic target for human CRC in the future.

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Identification of circular RNA hsa_circ_0044556 and its effect on the development and progression of colorectal cancer

10.21203/rs.3.rs-26944/v1 ◽

2020 ◽

Author(s):

Liang Jing ◽

Junhui Wu ◽

Xiaocheng Tang ◽

Min Ma ◽

Fei Long ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Lines ◽

Tumor Stage ◽

Circular Rna ◽

Gene Expression Omnibus ◽

Migration And Invasion ◽

Circular Rnas ◽

Normal Tissues ◽

Node Metastasis

Abstract Background Circular RNAs (circRNAs) are a novel class of noncoding RNAs. Increasing evidence indicates that circRNAs play an important role in the occurrence and development of tumors. However, the role of circRNAs in the development and progression of colorectal cancer (CRC) remains unclear. Methods First, we searched for differentially expressed circRNAs using a circRNA microarray in paired CRC and adjacent normal tissues. The circRNA hsa_circ_0044556 was screened out from the existing CRC circRNA microarray in the Gene Expression Omnibus database and our microarray. The clinical significance of hsa_circ_0044556 expression level in CRC patients was then investigated. Finally, the functions of the targets of this circRNA were determined in CRC cell lines. Results hsa_circ_0044556 was highly expressed in CRC patients and was positively correlated with tumor stage and lymph node metastasis. In CRC cell lines, the proliferation, migration, and invasion of cancer cells were inhibited by knocking down hsa_circ_0044556 expression. Conclusion hsa_circ_0044556 promoted the development and progression of CRC. It is possible that hsa_circ_0044556 will become a novel biomarker or therapeutic target for CRC.

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