scholarly journals lncRNA TUG1-Mediated Mir-142-3p Downregulation Contributes to Metastasis and the Epithelial-to-Mesenchymal Transition of Hepatocellular Carcinoma by Targeting ZEB1

2018 ◽  
Vol 48 (5) ◽  
pp. 1928-1941 ◽  
Author(s):  
Chuan He ◽  
Zhigang Liu ◽  
Li Jin ◽  
Fang Zhang ◽  
Xinhao Peng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Background/Aims: MicroRNA-142-3p (miR-142-3p) is dysregulated in many malignancies and may function as a tumor suppressor or oncogene in tumorigenesis and tumor development. However, few studies have investigated the clinical significance and biological function of miR-142-3p in hepatocellular carcinoma (HCC). Methods: The expression levels of taurine upregulated gene 1 (TUG1), miR-142-3p, and zinc finger E-box-binding homeobox 1 (ZEB1) were evaluated in HCC tissues and cell lines by quantitative real-time PCR. MTT and colony formation assays were used to detect cell proliferation ability, transwell assays were used to assess cell migration and invasion, and luciferase reporter assays were used to examine the interaction between the long noncoding RNA TUG1 and miR-142-3p. Tumor formation was evaluated through in vivo experiments. Results: miR-142-3p was significantly downregulated in HCC tissues, but TUG1 was upregulated in HCC tissues. Knockdown of TUG1 and upregulation of miR-142-3p inhibited cell proliferation, cell migration, cell invasion, and the epithelial-mesenchymal transition (EMT). miR-142-3p was found to be a prognostic factor of HCC, and the mechanism by which TUG1 upregulated ZEB1 was via direct binding to miR-142-3p. In vivo assays showed that TUG1 knockdown suppressed cell proliferation and the EMT in nude mice. Conclusion: The results of this study suggest that the TUG1/miR-142-3p/ ZEB1 axis contributes to the formation of malignant behaviors in HCC.

scholarly journals Downregulation of circ_0037655 impedes glioma formation and metastasis via the regulation of miR-1229-3p/ITGB8 axis

2021 ◽  
Vol 16 (1) ◽  
pp. 442-454
Author(s):  
Wenhui Zou ◽  
Yalei Cao ◽  
Kai Cheng ◽  
Changyu Li ◽  
Fu Zhu ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Mesenchymal Transition ◽  
Circular Rna ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Scratch Assay ◽  
Mesenchymal Transition ◽  
Glioma Progression

Abstract Background Glioma is the most frequent, highly aggressive primary intracranial malignant tumor. Circular RNA (circRNA) circ_0037655 has been reported to be a vital regulator in glioma. The different functional mechanism behind circ_0037655 was investigated in the current study. Methods The expression of circ_0037655, microRNA-1229-3p (miR-1229-3p) and integrin beta-8 (ITGB8) was detected via the quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Cellular research was performed via colony formation assay for cell proliferation, flow cytometry for cell cycle and cell apoptosis, scratch assay for cell migration, as well as transwell assay for cell migration and invasion. Western blot was used for detection of ITGB8 protein and epithelial–mesenchymal transition (EMT) process. Dual-luciferase reporter assay was implemented for the binding analysis of potential targets. In vivo assay was administered via xenograft in mice. Results Upregulation of circ_0037655 was affirmed in glioma samples and cells. Tumor formation and metastasis of glioma were inhibited after circ_0037655 was downregulated. miR-1229-3p acted as a target of circ_0037655, and its upregulation was responsible for the function of si-circ_0037655 in glioma cells. miR-1229-3p functioned as a tumor inhibitor in glioma progression by targeting ITGB8. circ_0037655 modulated the ITGB8 expression by targeting miR-1229-3p. In vivo knockdown of circ_0037655 also suppressed glioma tumorigenesis by acting on the miR-1229-3p/ITGB8 axis. Conclusion This study showed that downregulation of the expression of circ_0037655 could inhibit glioma progression by acting on the miR-1229-3p/ITGB8 axis. The specific circ_0037655/miR-1229-3p/ITGB8 axis was disclosed in glioma research.

scholarly journals microRNA-802 inhibits epithelial-mesenchymal transition through targeting flotillin-2 in human prostate cancer

2017 ◽  
Vol 37 (2) ◽  
Author(s):  
Dawei Wang ◽  
Guoliang Lu ◽  
Yuan Shao ◽  
Da Xu
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Epithelial Mesenchymal Transition ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition

miRNAs are a class of non-coding RNAs that exert critical roles in various biological processes. The aim of the present study was to identify the functional roles of miR-802 in regulating epithelial–mesenchymal transition (EMT) in prostate cancer (PCa). miR-802 expression was detected in 73 pairs of PCa samples and PCa cell lines (PC3 and DU145 cells) by qRT-PCR. Cell proliferation was detected using MTT assay, and cell apoptosis was evaluated using flow cytometry. Transwell assay was conducted to investigate cell migration and invasion. Expression analysis of a set of EMT markers was performed to explore whether miR-802 is involved in EMT program. Xenograft model was established to investigate the function of miR-802 in carcinogenesis in vivo. The direct regulation of Flotillin-2 (Flot2) by miR-802 was identified using luciferase reporter assay. miR-802 was remarkably down-regulated in PCa tissues and cell lines. Gain-of-function trails showed that miR-802 serves as an ‘oncosuppressor’ in PCa through inhibiting cell proliferation and promoting cell apoptosis in vitro. Overexpression of miR-802 significantly suppressed in vivo PCa tumor growth. Luciferase reporter analysis identified Flot2 as a direct target of miR-802 in PCa cells. Overexpressed miR-802 significantly suppressed EMT, migration and invasion in PCa cells by regulating Flot2. We identified miR-802 as a novel tumor suppressor in PCa progression and elucidated a novel mechanism of the miR-802/Flot2 axis in the regulation of EMT, which may be a potential therapeutic target.

scholarly journals MiR-93 suppresses cell proliferation and invasion by targeting ZNF322 in human hepatocellular carcinoma

2021 ◽  
Author(s):  
Yong Zhang ◽  
Liangsheng Miao ◽  
Huijuan Zhang ◽  
Gang Wu ◽  
Jianrui Lv
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Overall Survival ◽  
Cell Migration ◽  
Tumor Growth ◽  
Colony Formation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Over Expression

IntroductionThis study aimed to investigate the biological role of microRNA 93 (miR-93), a novel tumor-related miRNA, in human hepatocellular carcinoma (HCC) and elucidate the potential molecular mechanisms involved.Material and methodsQuantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine the expression of miR-93 in HCC tissues and cell lines. The log-rank test and Kaplan-Meier survival analysis were performed to evaluate the relationship between miR-93 expression and overall survival. MTT assay, colony formation assay, Transwell migration and invasion assays were carried out to exam cell proliferation, colony formation, migration and invasion, respectively. Murine xenograft models were established to the effect of miR-93 on tumor growth in vivo. TargetScan online software was applied to predict the potential target of miR-93. Luciferase reporter assays were used to validate the direct binding of miR-93 and its putative target.ResultsHere we found that miR-93 was significantly down-regulated in HCC tissues and cell lines. Patients with decreased miR-93 expression had a significantly shorter overall survival. Functional investigations demonstrated miR-93 over-expression suppressed HCC cell proliferation, weakened clonogenic ability, and slowed down cell migration and invasion; whereas miR-93 depletion facilitated HCC cell proliferation, colony formation, cell migration and invasion. MiR-93 over-expression retarded tumor growth in vivo. Luciferase reporter assay and rescue assay revealed that zinc finger protein 322 (ZNF322) was a direct target of miR-93 and mediated the inhibitory effects of miR-93 on HCC cell proliferation and motility.ConclusionsOur data may provide some evidence for miR-93/ZNF322 axis a candidate therapeutic target for HCC.

Downregulation of long noncoding RNA T1NCR inhibits cell proliferation, invasion, and epithelial-mesenchymal transition of hepatocellular carcinoma

2021 ◽  
Vol 7 (6) ◽  
pp. 6499-6510
Author(s):  
Hongjuan Li ◽  
Yaqin Chen ◽  
Chunyan Wu ◽  
Haiyan Zhao ◽  
Xuesong Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Normal Tissues ◽  
Proliferation Ability ◽  
Non Coding Rnas

Accumulating reports have identified that long non-coding RNAs (IncRNAs) function as key regulators of tumor initiation and progression. The aim of the current study was to determine the clinical significance and functional role of TINCR in hepatocellular carcinoma (HCC). In the present study, the level of IncRNA TINCR expression was significantly upregulated in HCC tissues compared to adjacent normal tissues. Higher levels of IncRNA TINCR expression were significantly correlated with tumor size and vascular invasion of HCC patients. LncRNA TINCR knockdown inhibited cell proliferation ability, increased the proportion of G1 phase cells, reduced the proportion of S phase cells, and suppressed cell invasion of HCC in vitro. Additionally, IncRNA TINCR knockdown inhibited the HCC cell epithelial-mesenchymal transition (EMT) phenomenon by upregulating E-cadherin and reducing N-cadherin expression. We demonstrated that knockdown of IncRNA reduced tumor growth in vivo. Thus, these results indicated that IncRNA TINCR exhibits a tumor oncogenic role in HCC and inhibition of IncRNA TINCR might serve as a therapeutic target for HCC.

scholarly journals The POU2F1/miR-4490/USP22 axis regulates cell proliferation and metastasis in gastric cancer

2020 ◽  
Vol 43 (6) ◽  
pp. 1017-1033 ◽  
Author(s):  
Yizhi Xiao ◽  
Side Liu ◽  
Jiaying Li ◽  
Weiyu Dai ◽  
Weimei Tang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Aberrant Expression ◽  
Mesenchymal Transition

Abstract Purpose Growing evidence indicates that aberrant expression of microRNAs contributes to tumor development. However, the biological role of microRNA-4490 (miR-4490) in gastric cancer (GC) remains to be clarified. Methods To explore the function of miR-4490 in GC, we performed colony formation, EdU incorporation, qRT-PCR, Western blotting, in situ hybridization (ISH), immunohistochemistry (IHC), flow cytometry, ChIP and dual-luciferase reporter assays. In addition, the growth, migration and invasion capacities of GC cells were evaluated. Results We found that miR-4490 was significantly downregulated in primary GC samples and in GC-derived cell lines compared with normal controls, and that this expression level was negatively correlated with GC malignancy. Exogenous miR-4490 expression not only reduced cell cycle progression and proliferation, but also significantly inhibited GC cell migration, invasion and epithelial-mesenchymal transition (EMT) in vitro. Mechanistically, we found that miR-4490 directly targets USP22, which mediates inhibition of GC cell proliferation and EMT-induced metastasis in vitro and in vivo. Moreover, we found through luciferase and ChIP assays that transcription factor POU2F1 can directly bind to POU2F1 binding sites within the miR-4490 and USP22 promoters and, by doing so, modulate their transcription. Spearman’s correlation analysis revealed a positive correlation between USP22 and POU2F1 expression and negative correlations between miR-4490 and USP22 as well as miR-4490 and POU2F1 expression in primary GC tissues. Conclusion Based on our results we conclude that miR-4490 acts as a tumor suppressor, and that the POU2F1/miR-4490/USP22 axis plays an important role in the regulation of growth, invasion and EMT of GC cells.

scholarly journals CircRNA circ_0004370 promotes cell proliferation, migration, and invasion and inhibits cell apoptosis of esophageal cancer via miR-1301-3p/COL1A1 axis

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 104-116
Author(s):  
Xiaobo Chen ◽  
Hongwen Sun ◽  
Yunping Zhao ◽  
Jing Zhang ◽  
Guosheng Xiong ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Ec Cells

AbstractBackgroundThe aim of this study was to investigate the circ_0004370 expression in EC, its effects on cell proliferation, apoptosis, migration, invasion, and epithelial–mesenchymal transition (EMT) process, and the underlying regulatory mechanisms in EC.MethodsThe protein levels of COL1A1 and EMT-related proteins were detected by western blot. The role of circ_0004370 on cell viability, proliferation, and apoptosis was analyzed by Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and flow cytometry, respectively. The transwell assay was used to examine cell migration and invasion. The binding sites between miR-1301-3p and circ_0004370 or COL1A1 were predicted by starbase software and confirmed by dual-luciferase reporter assay and RNA pull-down assay.ResultsWe discovered that circ_0004370 was remarkably upregulated in EC tissues and cells. Knockdown of circ_0004370 inhibited cell proliferation, migration as well as invasion, and promoted apoptosis in vitro, while its effect was rescued by miR-1301-3p inhibition. And circ_0004370 mediated the EMT process in EC cells. Moreover, we explored its regulatory mechanism and found that circ_0004370 directly bound to miR-1301-3p and COL1A1 was verified as a target of miR-1301-3p. COL1A1 was highly expressed in EC cells and upregulation of COL1A1 reversed the effects of miR-1301-3p on cell proliferation, migration, invasion, and apoptosis. In addition, silencing of circ_0004370 reduced tumor volumes and weights in vivo. We showed that circ_0004370/miR-1301-3p/COL1A1 axis played the critical role in EC to regulate the cell activities.ConclusionCirc_0004370 promotes EC proliferation, migration and invasion, and EMT process and suppresses apoptosis by regulating the miR-1301-3p/COL1A1 axis, indicating that circ_0004370 may be used as a potential therapeutic target for EC.

scholarly journals miR-186 Suppresses the Progression of Cholangiocarcinoma Cells Through Inhibition of Twist1

2019 ◽  
Vol 27 (9) ◽  
pp. 1061-1068 ◽  
Author(s):  
Ming Zhang ◽  
Baochang Shi ◽  
Kai Zhang
Keyword(s):  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Formation ◽  
In Vitro Assays ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Cycle Arrest

Deregulation of miR-186 and Twist1 has been identified to be involved in the progression of multiple cancers. However, the detailed molecular mechanisms underlying miR-186-involved cholangiocarcinoma (CCA) are still unknown. In this study, we found that miR-186 was downregulated in CCA tissues and cell lines, and negatively correlated with the expression of Twist1 protein. In vitro assays demonstrated that miR-186 mimics repressed cell proliferation, in vivo tumor formation, and caused cell cycle arrest. miR-186 mimics also inhibited the migration and invasion of CCLP1 and SG-231 cells. Mechanistically, the 3′-untranslated region (3′-UTR) of Twist1 mRNA is a direct target of miR-186. Further, miR-186 inhibited the expressions of Twist1, N-cadherin, vimentin, and matrix metallopeptidase 9 (MMP9) proteins, whereas it increased the expression of E-cadherin in CCLP1 and SG-231 cells. Silencing of Twist1 expression enhanced the inhibitory effects of miR-186 on the proliferation, migration, and invasion of CCLP1 and SG-231 cells. In conclusion, miR-186 inhibited cell proliferation, migration, invasion, and epithelial‐mesenchymal transition (EMT) through targeting Twist1 in human CCA. Thus, miR-186/Twist1 axis may benefit the development of therapies for CCA.

Exposure to desflurane anesthesia confers colorectal cancer cells metastatic capacity through deregulation of miR-34a/LOXL3 

2020 ◽  
Author(s):  
Junyi Ren ◽  
Xiaopeng Wang ◽  
Gang Wei ◽  
Yajing Meng
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Protective Role ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Elevated Expression ◽  
Public Datasets

Abstract Background: Due to high potency and low toxicity, desflurane has been wildly used during surgery. Recent evidence that the use of desflurane was associated with colorectal cancer (CRC) tumor metastasis and poor prognosis raising concerns about the safety of desflurane. However, the mechanism was uncovered.Methods: CRC cells were exposed to desflurane, the changes in morphology and epithelial-mesenchymal transition (EMT)-related genes were evaluated. Transwell assay was used to study the migration and invasion effect. Xenograft was performed to study the tumor formation ability of desflurane-treated cells in vivo. Dual luciferase reporter assay was conducted to verify the target of miR-34a. Knockdown or overexpression of LOXL3 was used to investigate the mechanism of desflurane-induced EMT. The association of LOXL3 with CRC molecular subtypes and clinical relevance was studied by analysis of public datasets. Results: Exposure to desflurane induced EMT, migration, and invasion in CRC cells. Mice injected with desflurane-treated cells formed more tumors in the lungs. Downregulation of miR-34a and upregulation of LOXL3 were required for desflurane-induced EMT in CRC cells. LOXL3 was a direct target of miR-34a. Overexpression of LOXL3 rescued miR-34a-repressed EMT after exposure to desflurane. Elevated expression of LOXL3 was enriched in CMS4 and CRIS-B subtypes. Patients with high expression of LOXL3 showed more lymph node metastasis, as well as poor survival.Conclusion: Desflurane induced EMT and metastasis in CRC through deregulation of miR-34a/LOXL3 axis. Clinical miR-34a mimic or inhibitor targeting LOXL3 might have a potential protective role when CRC patients anesthetized by desflurane.

scholarly journals Upregulation of Long Non-Coding RNA PlncRNA-1 Promotes Metastasis and Induces Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma

2016 ◽  
Vol 38 (2) ◽  
pp. 836-846 ◽  
Author(s):  
Liyang Dong ◽  
Junwei Ni ◽  
Wenhao Hu ◽  
Chang Yu ◽  
Haiyan Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Clinicopathological Characteristics ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Normal Tissues ◽  
Promote Tumor Growth

Background/Aims: PlncRNA-1 has been demonstrated to promote malignancy in various cancers. The present study aims to investigate the expression pattern, prognosis value and the function of PlncRNA-1 in human hepatocellular carcinoma (HCC). Methods: The expression of PlncRNA-1 in 84 pairs of HCC and their matched normal tissues was examined by quantitative real-time polymerase chain reaction (qRT-PCR). The correlations of PlncRNA-1 expression and clinicopathological characteristics and prognosis were also analyzed. The biological role of PlncRNA-1 in cell proliferation, migration and invasion was examined in vitro and in vivo. Results: The results showed that the level of PlncRNA-1 expression was significantly increased in HCC tissues and significantly correlated with tumor size, vascular invasion and advanced TNM stage. Moreover, patients with high levels of PlncRNA-1 expression had relatively poor prognostic outcomes, serving as an independent prognostic factor for HCC. In vitro functional assays indicated that knockdown of PlncRNA-1 expression significantly reduced cell proliferation, migration and invasion by inhibiting the epithelial-mesenchymal transition (EMT) signaling. Animal model experiments confirmed the ability of PlncRNA-1 to promote tumor growth in vivo. Conclusions: Taken together, our findings suggest that PlncRNA-1 may serve as an oncogene in HCC progression and represent a valuable prognostic marker and potential therapeutic target for HCC.

scholarly journals LincHOXA10 Facilitates Colorectal Cancer Development By Regulating HOXA10-Mediated Epithelial-Mesenchymal Transtion

2020 ◽  
Author(s):  
Huifang Zhu ◽  
Yongzhen Li ◽  
Yinghui Zhang ◽  
Zheying Zhang ◽  
Yongxia Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Tumor Formation ◽  
Migration And Invasion ◽  
Tissue Samples ◽  
Mesenchymal Transition

Abstract Background: Long non-coding RNAs (lncRNAs) have been reported to play an important role in tumorigenesis and metastasis of human colorectal cancer (CRC). However, the specific role of LincHOXA10 in CRC remains unknown.Methods: The expression of LincHOXA10 and HOXA10 in CRC cells and tissue samples was measured by quantitative reverse transcription PCR (qRT-PCR). The protein expression of HOXA10, E-cadherin, N-cadherin, Vinmentin, p-smad2 and p-smad3 was assessed by Western blotting or immunofluorescence staining. Cell proliferation, migration, and invasion were assessed by the MTT and transwell assays. Tumor growth in vivo was carried out by subcutaneous tumor formation in nude mice.Results: In the present study, we found that LincHOXA10 expression was significantly higher in human CRC tissues than the paired normal tissues. In fact, LincHOXA10 level correlated with the CRC tumor sizes and lymphatic metastasis. In cultured CRC cells, knockdown of LincHOXA10 inhibited cell proliferation, migration and invasion. LincHOXA10 deficiency also attenuated CRC tumor growth in vivo. Mechanistically, LincHOXA10 interacted with HOXA10 and regulated its expression. HOXA10 levels were interrelated to the LincHOXA10 level in CRC cells. Functionally, HOXA10 was essential for TGF-β1/SMADs-induced epithelial -mesenchymal transition of CRC cells, and HOXA10 played a critical role in mediating the function of LincHOXA10. Importantly, HOXA10 expression was significantly up-regulated in human CRC tissues.Conclusions: LincHOXA10 facilitates CRC development and metastasis via regulating HOXA10-mediated epithelial-mesenchymal transition of CRC cells.

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