MiR-188-3p and miR-133b Suppress Cell Proliferation in Human Hepatocellular Carcinoma via Post-Transcriptional Suppression of NDRG1

Background: Previous studies reported that N-myc downstream-regulated gene 1 (NDRG1) was upregulated in various cancer tissues and decreased expression of miR-188-3p and miR-133b could suppress cell proliferation, metastasis, and invasion and induce apoptosis of cancer cells. However, the molecular mechanism of NRDG1 involved in hepatocellular carcinoma (HCC) tumorigenesis is still unknown. Methods: The expressions of miR-188-3p, miR-133b, and NRDG1 in HCC tissues and cells were quantified by qRT-PCR and Western blot. MTT assay and transwell invasion assay were performed to evaluate cell growth and cell migration, respectively. Luciferase reporter assay were performed to determine whether miR-188-3p and miR-133b could directly bind to NRDG1 in HCC cells. Results: The results showed that NRDG1 was upregulated and these 2 microRNAs were downregulated in HCC tissues. NRDG1 was negatively correlated with miR-188-3p and miR-133b in HCC tissues. MiR-188-3p and miR-133b were demonstrated to directly bind to 3′UTR of NRDG1 and inhibit its expression. Upregulation of miR-188-3p and miR-133b reduced NRDG1 expression in hepatocellular carcinoma cell lines, which consequently inhibited cell growth and cell migration. Conclusions: Our finding suggested that miR-188-3p and miR-133b exert a suppressive effect on hepatocellular carcinoma proliferation, invasion, and migration through downregulation of NDRG1.

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miR-340 Inhibits the Development of Hepatocellular Carcinoma by Down-Regulating Akt Signaling Pathway

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2590 ◽

2021 ◽

Vol 11 (9) ◽

pp. 1785-1791

Author(s):

Tangpeng Xu ◽

Changli Ruan ◽

Xu Bin ◽

Mengxue Hu

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Signaling Pathway ◽

Akt Signaling ◽

Pathological Grade ◽

Akt Signaling Pathway ◽

Invasion And Migration ◽

Proliferation Ability ◽

And Migration ◽

Cancer Tissues

Hepatocellular carcinoma (HCC) is a serious threat to human health. miR-340 participates in HCC pathogenesis, but its specific mechanism is not completely clear. Therefore, our study assessed the mechanism by how miR-340 involves in HCC. The cancer tissues and paracancerous tissues of HCC patients were collected. miR-340 mimics/NC and Akt siRNA were transfected into HepG2 cells followed by analysis of miR-304 and EMT-related molecules expression by Real-time PCR, cell invasion and migration by Transwell assay, cell proliferation ability by CCK8 assay as well as p-Akt and p-mTOR level by Western blot. miR-340 in HCC tissues was significantly downregulated compared to adjacent tissues (P <0.001). With increased pathological grade, miR-340 expression was decreased gradually. p-Akt and p-mTOR in HCC tissues was significantly upregulated and elevated gradually with increased pathological grade. p-Akt and p-mTOR was negatively associated with miR-340 (P <0.001). After overexpression of miR-340, HepG2 cell proliferation, invasion, migration and epithelialization were significantly inhibited, and p-Akt and p-mTOR was reduced. When Akt expression was interfered with siRNA, cell proliferation and epithelialization was further inhibited. miR-340 inhibits the development of hepatocellular carcinoma through Akt signaling pathway.

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MicroRNA-517c Functions as a Tumor Suppressor in Hepatocellular Carcinoma via Downregulation of KPNA2 and Inhibition of PI3K/AKT Pathway

Journal of Healthcare Engineering ◽

10.1155/2022/7026174 ◽

2022 ◽

Vol 2022 ◽

pp. 1-9

Author(s):

Limin Ma ◽

Changming Tao ◽

Yingying Zhang

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Epithelial To Mesenchymal Transition ◽

Clinical Analysis ◽

Luciferase Reporter ◽

Akt Pathway ◽

Tissue Samples ◽

Mesenchymal Transition ◽

Invasion And Migration ◽

And Migration

Objective. Hepatocellular carcinoma (HCC) is a kind of solid and highly aggressive malignant tumor with poor prognosis. MicroRNA (miRNA/miR) has been confirmed to be involved in HCC development. The current study focused on the functions and mechanisms of miR-517c in HCC. Methods. Expressions of miR-517c and Karyopherin α2 (KPNA2) mRNA in HCC cell lines and tissue samples were examined using quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was conducted for detections of epithelial-to-mesenchymal transition (EMT) and PI3K/AKT markers. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Transwell assays were utilized to investigate the influence of miR-517c on HCC cell proliferation, invasion, and migration. TargetScan and luciferase reporter assay were performed to search for the potential target gene of miR-517c. Results. We demonstrated that miR-517c expressions were decreased in HCC tissues and cells. Moreover, the clinical analysis showed that decreased miR-517c expressions in HCC tissues correlated with shorter overall survival and malignant clinicopathologic features of HCC patients. MTT assay showed that miR-517c upregulation prominently repressed HCC cell proliferation. In addition, miR-517c restoration could significantly suppress HCC cell invasion and migration as demonstrated by Transwell assays. We also found that miR-517c directly targeted KPNA2 and regulated the PI3K/AKT pathway and EMT, exerting prohibitory functions in HCC. Conclusion. Taken together, this study stated that miR-517c inhibited HCC progression via regulating the PI3K/AKT pathway and EMT and targeting KPNA2 in HCC, providing a novel insight into HCC treatment.

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MiR-566 mediates cell migration and invasion in colon cancer cells by direct targeting of PSKH1

Cancer Cell International ◽

10.1186/s12935-019-1053-1 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Ying Zhang ◽

Siqi Zhang ◽

Jian Yin ◽

Ruisi Xu

Keyword(s):

Cell Proliferation ◽

Cell Growth ◽

Cell Survival ◽

Cell Lines ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Invasion And Migration ◽

Reporter Assays ◽

And Migration ◽

Colon Epithelial Cell

Abstract Background Colorectal cancer (CRC), a common malignancy worldwide, and microRNAs (miRs) have been suggested to play roles in the disease. MiR-566 expression has been shown to be reduced in CRC, but its functions and mechanisms are still unclear. Methods Cell viability was assessed by using the CellTiter 96 AQueous One Solution Cell Proliferation kit. Cell proliferation was measured with MTT assay. Cell metastasis were measured by transwell assay. Luciferase reporter assays was used to confirm the target of MiR-566. PSKH1 expression was measured by RT-PCR and western blot. Results In the present study, we first observed that miR-566 was expressed in several CRC cell lines (SW480, SW620, LoVo, HT29 and Caco-2) at low levels compared to control colon epithelial cell lines (FHC). Further study showed that miR-566 overexpression suppressed cell survival and impeded cell proliferation, whereas inhibition of its expression enhanced cell survival and proliferation. Transwell assays showed that cell invasion and migration were reduced in cells overexpressing miR-566 and increased in those with inhibition of miR-566. Further analysis confirmed that PSKH1 is a target of miR-566. MiR-566 overexpression significantly inhibited PSKH1 expression and reintroduction of PSKH1 partially reversed the effects of miR-566 on CRC cell growth and metastasis in SW480 and Caco-2 cells. Conclusions Taken together, the data show that CRC cell growth and metastasis can be significantly suppressed by miR-566 through targeting PSKH1.

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lncRNA-ENST00000513396 is associated with multiple tumor signaling pathways, promotes the cell proliferation, invasion and migration in colorectal cancer

10.21203/rs.3.rs-309313/v1 ◽

2021 ◽

Author(s):

Jinxin Zhu ◽

Hui Wang ◽

Yangbin Du ◽

Zhenyu He

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Cell Migration ◽

Signaling Pathways ◽

Cell Invasion ◽

Tumor Cell Proliferation ◽

Invasion And Migration ◽

Multiple Tumor ◽

And Migration ◽

Cancer Tissues

Abstract Purpose Recently, many studies have revealed that Long noncoding RNAs (lncRNAs) were abundant in kinds of cells and might have multiple functions in a wide range of biological processes, such as proliferation, apoptosis, or cell migration. However, the role of lncRNA in the development of colorectal cancer has not been systematically reported and needs to be studied. Methods We applied Agilent microarray in tumoral tissues and paired para-cancer tissues for detecting different expression of lncRNAs and mRNAs. Bioinformatics analysis were used to identify the relationship between lncRNAs and corresponding mRNAs and the potential function of the lncRNAs. lncRNA-ENST00000430471 was chosen for further functional study through constructing overexpression plasmid, cell invasion, and cell migration. Results We found that 460 lncRNAs were significantly deregulated in cancer tissues. More importantly, they may participate in a variety of tumor-related signaling pathways through functional enrichment analysis with their co-expressed mRNAs, suggesting that these lncRNAs might play critical roles in tumorigenesis and development. Recently, we found lncRNA-ENST00000513396 was significantly upregulated in cancer tissues compared with para-cancer tissues. The overexpression of ENST00000513396 promotes tumor cell proliferation. Meanwhile ENST00000430471 could promote migration and invasion ability of colorectal cells. Conclusion LncRNAs play an important role in the development of colorectal cancer. Differentially expressed lncRNAs are associated with multiple tumor signaling pathways. Overexpression of lncRNA- ENST00000513396 in colorectal cancer cells can promote tumor cell proliferation and increase the ability of cell invasion and migration, which leads to the development of tumor.

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PCGEM1 Promotes Proliferation, Migration And Invasion In Prostate Cancer By Sponging miR-506 To Upregulate TRIAP1

10.21203/rs.3.rs-878010/v1 ◽

2021 ◽

Author(s):

He Liu ◽

Xin He ◽

Tianjiao Li ◽

Yi Qu ◽

Lina Xu ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Proliferation ◽

Noncoding Rna ◽

Suppressive Effect ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Invasion And Migration ◽

Gene Level ◽

And Migration

Abstract Background: The important role of long noncoding RNAs (lncRNAs) in cancer has been demonstrated in many studies. Prostate cancer gene expression marker 1 (PCGEM1) is a lncRNA specifically expressed within the prostate and overexpressed in many cancer cells. Numerous studies have shown that PCGEM1 promotes cell proliferation, invasion and migration. However, the specific mechanism of PCGEM1 within prostate cancer (PCa) has not been elucidated. MicroRNA-506-3p (miR-506-3p) is a noncoding RNA, and studies have indicated that miR-506-3p is downregulated in prostate cancer cell lines and functions as a tumor suppressor.Methods: The TCGA (GEPIA) database (http://gepia.cancer-pku.cn/) was employed to measure PCGEM1 levels in PCa. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the PCGEM1 gene level. CCK-8 (Cell Counting Kit-8) and colony formation assays were used to detect cell proliferation, and Transwell assays were applied to assess cell invasion and migration. The interacting ability of miR-506-3p with PCGEM1 or TRIAP1 was validated through a dual-luciferase reporter assay. TRIAP1 protein expression was detected by Western blotting.Results: PCGEM1 expression was increased in PCa tissues and cells. In PCa tissues, High PCGEM1 expression was associated with high Gleason score, distant metastasis and extracapsular extension. In addition, PCGEM1 knockdown inhibited PCa cell (C4-2B and PC-3) proliferation, invasion and migration. miR-506-3p may interact with PCGEM1 or TRIAP1, and the suppressive effect of PCGEM1 knockdown was reversed when TRIAP1 or a miR-506-3p inhibitor was cotransfected.Conclusion: PCGEM1 expression increased in PCa cells and tissues, enhancing PCa cell proliferation, migration and invasion by sponging miR-506 to upregulate TRIAP1.

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miR-206 inhibits cell proliferation, invasion, and migration by down-regulating PTP1B in hepatocellular carcinoma

Bioscience Reports ◽

10.1042/bsr20181823 ◽

2019 ◽

Vol 39 (5) ◽

Cited By ~ 6

Author(s):

Qian Yang ◽

Lunli Zhang ◽

Yuanbin Zhong ◽

Lingling Lai ◽

Xiaopeng Li

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Tyrosine Phosphatase ◽

Tumor Development ◽

Luciferase Reporter ◽

Mice Model ◽

Invasion And Migration ◽

Huh7 Cells ◽

And Migration

Abstract Protein tyrosine phosphatase 1B (PTP1B) has been reported as an oncogene in hepatocellular carcinoma (HCC). However, how PTP1B is regulated in HCC remains unclear. MicroRNAs (miRNAs) are a class of small non-coding RNAs involved many biological processes including tumorigenesis. In this study, we investigated whether miRNA participated in the regulation of PTP1B in HCC. We found that miR-206, which was down-regulated during tumorigenesis, inhibited HCC cell proliferation and invasion. Overexpression of miR-206 inhibited proliferation, invasion, and migration of HCC cell lines HepG2 and Huh7. Mechanistically, we demonstrated that miR-206 directly targeted PTP1B by binding to the 3′-UTR of PTP1B mRNA as demonstrated by the luciferase reporter assay. Overexpression miR-206 inhibited PTP1B expression while miR-206 inhibition enhanced PTP1B expression in HepG2 and Huh7 cells. Functionally, the regulatory effect on cell proliferation/migration/invasion of miR-206 was reversed by PTP1B overexpression. Furthermore, tumor inoculation nude mice model was used to explore the function of miR-206 in vivo. Our results showed that overexpression of miR-206 drastically inhibited tumor development. In summary, our data suggest that miR-206 inhibits HCC development by targeting PTP1B.

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Knockdown CYP2S1 inhibits lung cancer cells proliferation and migration

Cancer Biomarkers ◽

10.3233/cbm-210189 ◽

2021 ◽

pp. 1-9

Author(s):

Huan Guo ◽

Baozhen Zeng ◽

Liqiong Wang ◽

Chunlei Ge ◽

Xianglin Zuo ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Cell Growth ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Lung Cancer Cells ◽

Invasion And Migration ◽

And Migration

BACKGROUND: The incidence of lung cancer in Yunnan area ranks firstly in the world and underlying molecular mechanisms of lung cancer in Yunnan region are still unclear. We screened a novel potential oncogene CYP2S1 used mRNA microassay and bioinformation database. The function of CYP2S1 in lung cancer has not been reported. OBJECTIVE: To investigate the functions of CYP2S1 in lung cancer. METHODS: Immunohistochemistry and Real-time PCR were used to verify the expression of CYP2S1. Colony formation and Transwell assays were used to determine cell proliferation, invasion and migration. Xenograft assays were used to detected cell growth in vivo. RESULTS: CYP2S1 is significantly up-regulated in lung cancer tissues and cells. Knockdown CYP2S1 in lung cancer cells resulted in decrease cell proliferation, invasion and migration in vitro. Animal experiments showed downregulation of CYP2S1 inhibited lung cancer cell growth in vivo. GSEA analysis suggested that CYP2S1 played functions by regulating E2F targets and G2M checkpoint pathway which involved in cell cycle. Kaplan-Meier analysis indicated that patients with high CYP2S1 had markedly shorter event overall survival (OS) time. CONCLUSIONS: Our data demonstrate that CYP2S1 exerts tumor suppressor function in lung cancer. The high expression of CYP2S1 is an unfavorable prognostic marker for patient survival.

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Amygdalin promotes the activity of T cells to suppress the progression of HBV-related hepatocellular carcinoma via the JAK2/STAT3 signaling pathway

BMC Infectious Diseases ◽

10.1186/s12879-020-05713-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ruoyu Wang ◽

Dong Zhang ◽

Kewei Sun ◽

Jianping Peng ◽

Wenfang Zhu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

T Cells ◽

T Cell ◽

Cell Viability ◽

Caspase 3 ◽

Invasion And Migration ◽

Ifn Γ ◽

And Migration ◽

Cellular Immune

Abstract Background Hepatitis B virus (HBV) infection is a high-risk factor of hepatocellular carcinoma (HCC). Cellular immune responses are essential for HCC development, and the CD4+ and CD8+ T subtypes are identified as the primary anti-tumor immune cells. In the study, we investigated the effect and mechanism of amygdalin in the cellular immune response in HBV-related HCC and HCC progression. Methods The cell proliferation was examined by MTT analysis. Cells metastasis ability was detected by Invasion and migration assays. Quantification of apoptotic cells was performed with Flow cytometer assay. The protein levels of p-STAT3, STAT3, p-JAK2, JAK2, caspase-3, cleaved caspase-3 were detected by performing immunoblotting assays. Results We demonstrate that amygdalin treatment could rescue the HBV-T cell viability and IFN-γ and TNF-αproduction. In HBV-T cells, the MFI levels of CD8+ are lower than that in NC-T cells. Moreover, the phosphorylation levels of STAT3 and JAK2 are higher in HBV-T cells, compared to those in NC-T cells, and then reduced by amygdalin treatment. Co-culture with HBV-T cells could reduce IFN-γ and TNF-α, production while increase IL-6 and IL-10 production in HepG2.2.15 cells; these alterations could be partially reversed by amygdalin pretreatment. Finally, co-culture with HBV-T cells significantly promoted the cell viability, inhibited the apoptosis, and promoted the migration of HepG2.2.15 cells, and these alterations could be partially reversed by amygdalin treatment. Conclusion Our findings provide a rationale for further studies on the functions and mechanism of amygdalin inhibiting HBV-related HCC cell proliferation, invasion, and migration via T cell-mediated tumor immunity.

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AC093797.1 as a Potential Biomarker to Indicate the Prognosis of Hepatocellular Carcinoma and Inhibits Cell Proliferation, Invasion, and Migration by Reprogramming Cell Metabolism and Extracellular Matrix Dynamics

Frontiers in Genetics ◽

10.3389/fgene.2021.778742 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xiaoling Liu ◽

Chenyu Wang ◽

Qing Yang ◽

Yue Yuan ◽

Yunjian Sheng ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Extracellular Matrix ◽

Cell Proliferation ◽

Overall Survival ◽

Biological Function ◽

Cell Metabolism ◽

Hub Genes ◽

Invasion And Migration ◽

And Migration

Purpose: The risk signature composed of four lncRNA (AC093797.1, POLR2J4, AL121748.1, and AL162231.4.) can be used to predict the overall survival (OS) of patients with hepatocellular carcinoma (HCC). However, the clinical significance and biological function of AC093797.1 are still unexplored in HCC or other malignant tumors. In this study, we aimed to investigate the biological function of AC093797.1 in HCC and screen the candidate hub genes and pathways related to hepatocarcinogenesis.Methods: RT-qPCR was employed to detect AC093797.1 in HCC tissues and cell lines. The role of AC093797.1 in HCC was evaluated via the cell-counting kit-8, transwell, and wound healing assays. The effects of AC093797.1 on tumor growth in vivo were clarified by nude mice tumor formation experiments. Then, RNA-sequencing and bioinformatics analysis based on subcutaneous tumor tissue was performed to identify the hub genes and pathways associated with HCC.Results: The expression of AC093797.1 decreased in HCC tissues and cell lines, and patients with low expressed AC093797.1 had poor overall survival (OS). AC093797.1 overexpression impeded HCC cell proliferation, invasion, and migration in vitro and suppressed tumor growth in vivo. Compared with the control group, 710 differentially expressed genes (243 upregulated genes and 467 downregulated genes) were filtered via RNA-sequencing, which mainly enriched in amino acid metabolism, extracellular matrix structure constituents, cell adhesion molecules cams, signaling to Ras, and signaling to ERKs.Conclusion: AC093797.1 may inhibit cell proliferation, invasion, and migration in HCC by reprograming cell metabolism or regulating several pathways, suggesting that AC093797.1 might be a potential therapeutic and prognostic marker for HCC patients.

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MiR-92a-3p promote s invasion and migration of hepatocellular carcinoma cells by targeting PTEN

10.21203/rs.3.rs-408247/v1 ◽

2021 ◽

Author(s):

Yilin Hu ◽

Huiling Sun ◽

Qiping Lu ◽

Hongliang Mei ◽

Rong Liu

Keyword(s):

Hepatocellular Carcinoma ◽

Mutation Frequency ◽

Biological Information ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Clinical Samples ◽

Luciferase Reporter Gene ◽

Invasion And Migration ◽

And Migration ◽

The Impact

Abstract Background MiR-92a-3p has been reported to play a part in hepatocellular carcinoma (HCC), a leading type of lethal cancer around the world. In this study, we explored the function and mechanism of miR-92a-3p in HCC. Methods Firstly, the expression of miR-92a-3p in HCC along with its relationship with PTEN was analyzed through biological information. To investigate the impact of miR-92a-3p on the migration and invasion of HCC cells, we performed scratch wound healing and transwell assays. Next, RT-qPCR, western blot and dual luciferase reporter gene assays were conducted to determine whether PTEN is targeted by miR-92a-3p, which was then verified through rescue assays. Afterwards, in vivo animal experiments were carried out to determine the function of miR-92a-3p in HCC tissues. As an established fact, PETN is an anti-oncogene with frequent mutation inactivation in human cancers. Thus, we used the database to predict the mutation of PETN and its mutation frequency. Finally, CRISPR-cas12a was applied to detect the R130Q mutation on PETN in HCC clinical samples. Results This study found that the migration and invasion of HCC could be suppressed by inhibiting miR-92a-3p, which regulates the proliferation, migration and invasion of HCC through the regulation of PETN. The bioinformatics analysis indicated higher mutation frequency of R130Q/G/L* site on the PETN gene, and greater impact of R130Q site mutation on the progression of HCC. CRISPR-cas12a detected 26 cases of R130Q mutations on PTEN in 40 HCC clinical samples Conclusion Collectively, this study revealed that miR-92a-3p promoted the invasion and migration of HCC by targeting PTEN, and that the stability of PETN also affected the development of HCC, which may enrich and deepen our knowledge on the progression of HCC.

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