scholarly journals miR-145 Contributes to the Progression of Cervical Carcinoma by Directly Regulating FSCN1

2019 ◽  
Vol 28 (9-10) ◽  
pp. 1299-1305 ◽  
Author(s):  
Li Ma ◽  
Ling-Ling Li
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cervical Carcinoma ◽  
Hela Cells ◽  
Underlying Mechanism ◽  
Luciferase Assay ◽  
Cancer Cell Proliferation ◽  
Expression Levels ◽  
Direct Target

The purpose of our study was to investigate the underlying mechanism and functional role of microRNA-145 (miR-145) in cervical cancer. In this study, quantitative real-time PCR (qRT-PCR) was used to detect miR-145 and FSCN1 expression levels in tissues and HeLa cells. Western blotting was performed to determine the protein level of FSCN1. The luciferase assay was used to verify the direct target of miR-145. The CCK-8 assay and 2D colony formation assays were performed to determine the effects of miR-145 mimics or FSCN1 silencing on cell proliferation. miR-145 expression levels were significantly down-regulated, while FSCN1 expression levels were significantly up-regulated in the cervical carcinoma tissues compared with their matched non-cancerous tissues. In addition, FSCN1 expression levels were negatively correlated to miR-145 in tissues. Next, FSCN1 was verified as the direct target of miR-145 in HeLa cells. Moreover, overexpression of miR-145 dramatically inhibited the proliferation of HeLa cells. The silencing of FSCN1 exhibited the similar patterns on cell proliferation as miR-145 overexpression. The miR-145/ FSCN1 axis contributes to the progression of cervical cancer by inhibition of cervical cancer cell proliferation.

scholarly journals Effect of miR-301a/PTEN pathway on the proliferation and apoptosis of cervical cancer

2019 ◽  
Vol 25 (4) ◽  
pp. 217-223 ◽  
Author(s):  
Li-na Peng ◽  
Wen-tian Shi ◽  
Huan-rong Feng ◽  
Chuan-yu Wei ◽  
Qi-nan Yin
Keyword(s):  
Cervical Cancer ◽  
Cervical Carcinoma ◽  
Hela Cells ◽  
Pten Expression ◽  
Cell Counting ◽  
Luciferase Assay ◽  
Loss Of Function ◽  
Reverse Pattern ◽  
Significant Difference ◽  
Direct Target

The aim of this study was to evaluate the effect of the miR-301a/PTEN pathway in cervical cancer. miR-301a and PTEN expression were measured by quantitative real-time PCR (qRT-PCR) in tissues samples and HeLa cells. PTEN protein level was determined by Western blotting. Dual reporter luciferase assay was performed to validate PTEN as a direct target of miR-301a. The gain- and loss-of function assay was performed by miR-301a overexpression and silencing. Cell proliferation was monitored by cell counting Kit-8 (CCK-8). Cell apoptosis was quantitated by flow cytometry. SPSS was used to analyze the significant difference in the treatments. miR-301a demonstrated a significantly higher expression in cervical carcinoma tissues compared with the paired non-carcinoma tissues ( n = 12), while PTEN expression was found to be significantly lower in cervical carcinoma tissues than their paired non-carcinoma tissues ( n = 12). In addition, PTEN was identified as the direct target of miR-301a. Moreover, overexpression of miR-301a significantly promoted HeLa cells proliferation and anti-apoptosis which had a reverse pattern after PTEN overexpression. Our results confirm PTEN as a direct target of miR-301a in HeLa cells and suggest that miR-301a/PTEN pathway contributes to the development and progression of cervical cancer.

TXNIP induced by MondoA, rather than ChREBP, suppresses cervical cancer cell proliferation, migration and invasion

2019 ◽  
Vol 167 (4) ◽  
pp. 371-377 ◽  
Author(s):  
Junhua Zhang ◽  
Xingbo Tian ◽  
Huifang Yin ◽  
Songshu Xiao ◽  
Shuijing Yi ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Hela Cells ◽  
Cervical Cancer Cell ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Cancer Cell Proliferation ◽  
Interacting Protein

Abstract Evidence has indicated the associations between thioredoxin-interacting protein (TXNIP) and cancers. However, the role of TXNIP in cervical cancer remains unclear. Hence, this study aims to investigate the role of TXNIP in regulating cervical cancer cell proliferation, migration and invasion. TXNIP expression can be regulated by either MondoA or ChREBP in a cell- or tissue- dependent manner. Thus, we also explored whether TXNIP expression in cervical cancer can be regulated by MondoA or ChREBP. Our results showed that TXNIP expression was decreased in cervical cancer cells (HeLa, SiHa, CaSki, MS751, C-33A). Furthermore, TXNIP overexpression inhibited cell proliferation, migration and invasion in HeLa cells, whereas TXNIP silencing exerted the opposite effect in C-33A cells. Moreover, TXNIP expression could be induced by MondoA, rather than ChREBP in HeLa cells. Additionally, MondoA overexpression inhibited cell proliferation, migration and invasion through upregulating TXNIP in HeLa cells. In summary, TXNIP induced by MondoA, rather than ChREBP, suppresses cervical cancer cell proliferation, migration and invasion. Our findings provide new ideas for the prevention and treatment of cervical cancer.

scholarly journals Nujiangexanthone A Inhibits Cervical Cancer Cell Proliferation by Promoting Mitophagy

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2858
Author(s):  
Jiling Feng ◽  
Anahitasadat Mansouripour ◽  
Zhichao Xi ◽  
Li Zhang ◽  
Gang Xu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Hela Cells ◽  
Cervical Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Cancer Cell Growth ◽  
Antitumor Effects ◽  
Bioactive Component ◽  
Lysosome Degradation

Nujiangexanthone A (NJXA), a bioactive component isolated from the leaves of Garcinia nujiangensis, has been reported to exhibit anti-inflammatory, antioxidant, and antitumor effects. Our previous work has shown that NJXA induced G0/1 arrest and apoptosis, thus suppressing cervical cancer cell growth. The present study provides new evidence that NJXA can induce cell death in HeLa cells by promoting mitophagy. We first identified that NJXA triggered GFP-LC3 and YFP-Parkin puncta accumulation, which are biomarkers of mitophagy. Moreover, NJXA degraded the mitochondrial membrane proteins Tom20 and Tim23 and mitochondrial fusion proteins MFN1 and MFN2, downregulated Parkin, and stabilized PINK1. Additionally, we revealed that NJXA induced lysosome degradation and colocalization of mitochondria and autophagosomes, which was attenuated by knocking down ATG7, the key regulator of mitophagy. Furthermore, since mitophagy is induced under starvation conditions, we detected the cytotoxic effect of NJXA in nutrient-deprived HeLa cells and observed better cytotoxicity. Taken together, our work contributes to the further clarification of the mechanism by which NJXA inhibits cervical cancer cell proliferation and provides evidence that NJXA has the potential to develop anticancer drugs.

scholarly journals MIR-301b-3p Promotes Lung Adenocarcinoma Cell Proliferation, Migration and Invasion by Targeting DLC1

2021 ◽  
Vol 20 ◽  
pp. 153303382199003
Author(s):  
Haitao Liu ◽  
Xingjie Ma ◽  
Niu Niu ◽  
Junjie Zhao ◽  
Chao Lu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Biological Properties ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Dlc1 Expression

Background: miR-301b-3p is reported in various human cancers for its abnormal expression, while the role and molecular mechanisms in lung adenocarcinoma (LUAD) remain unclear, and this is the focus of the present study. Materials and Methods: TCGA database was consulted to know gene expression in LUAD tissue. CCK-8, colony formation assay and Transwell assay were applied to identify the role of target genes in regulating LUAD cell biological properties. Bioinformatics analysis plus dual-luciferase assay were performed to validate the potential connection between genes. Results: miR-301b-3p and DLC1 were the target genes of this study and respectively differentially up-regulated and down-regulated in LUAD. Functional experiments indicated that miR-301b-3p contributed to cancer cell proliferation, migration and invasion, while this effect was reversed with overexpressed DLC1 which was identified as a direct target of and regulated by miR-301b-3p. Conclusions: Collectively, miR-301b-3p was identified to actively function on LUAD malignant progression by suppressing DLC1 expression. This discovery provides a novel therapeutic strategy for LUAD patients, which helps improve the survival of patients.

scholarly journals METTL3 Promotes Lung Adenocarcinoma Tumorigenesis and Inhibits Ferroptosis by Stabilizing SLC7A11 m6A Modification

2021 ◽  
Author(s):  
Yiming Xu ◽  
Dandan Lv ◽  
Chao Yan ◽  
Hua Su ◽  
Xue Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Rna Stability ◽  
Underlying Mechanism ◽  
Rna Immunoprecipitation ◽  
Direct Target ◽  
Novel Target

Abstract Background: N6-methyladenosine (m 6 A) has emerged as a significant regulator of the progress of various cancers. However, its role in lung adenocarcinoma (LUAD) remains unclear. Here, we explored the biological function and underlying mechanism of methyltransferase-like 3 (METTL3), the main catalyst of m 6 A, in LUAD progression. Methods: The expression of m 6 A, METTL3, YTHDF1 and SLC7A11 were detected by immunochemistry or/and online datasets in LUAD patients. The effects of METTL3 on LUAD cell proliferation, apoptosis and ferroptosis were assessed through in vitro loss-and gain-of-function experiments. The in vivo effect on tumorigenesis of METTL3 was evaluated using the LUAD cell xenograft mouse model. MeRIP-seq, RNA immunoprecipitation and RNA stability assay were conducted to explore the molecular mechanism of METTL3 in LUAD. Results: The results showed that the m 6 A level, as well as the methylase METTL3 were both significantly elevated in LUAD patients and lung cancer cells. Functionally, we found that METTL3 could promote proliferation and inhibit ferroptosis in different LUAD cell models, while METTL3 knockdown suppressed LUAD growth in cell-derived xenografts. Mechanistically, solute carrier 7A11 (SLC7A11), the subunit of system Xc - , was identified as the direct target of METTL3 by mRNA-seq and MeRIP-seq. METTL3-mediated m 6 A modification could stabilize SLC7A11 mRNA and promote its translation, thus promoting LUAD cell proliferation and inhibiting cell ferroptosis, a novel form of programmed cell death. Additionally, we demonstrated that YTHDF1, a m 6 A reader, was recruited by METTL3 to enhance SLC7A11 m 6 A modification. Moreover, the expression of YTHDF1 and SLC7A11 were positively correlated with METTL3 and m 6 A in LUAD tissues.Conclusions: These findings reinforced the oncogenic role of METTL3 in LUAD progression and revealed its underlying correlation with cancer cell ferroptosis; these findings also indicate that METTL3 is a promising novel target in LUAD diagnosis and therapy.

scholarly journals Hsa_circ_0005909 promotes cell proliferation of osteosarcoma cells by targeting miR-338-3p/HMGA1 axis

2020 ◽  
Author(s):  
Cailong Zhang ◽  
Na Na ◽  
Li Liu ◽  
Yingzhu Qiu
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Pediatric Population ◽  
Luciferase Assay ◽  
Osteosarcoma Cells ◽  
Quantitative Real Time Pcr ◽  
Cell Clones ◽  
Dual Inhibition ◽  
Direct Target

Abstract Objective: Osteosarcoma (OS) is the most common malignant bone tumor in pediatric population. The main goal of this study is to investigate the role of has_circ_0005909 and the underlying signaling pathway involved in OS.Methods: Cell proliferation was measured using CCK-8 assay kit and clone formation assay. Change of RNA and protein expression was determined using RNA extract and quantitative real time PCR (RT-qPCR) assay and Western blotting, respectively. CircInteractome was used to predict the target of circRNA and starBase v2.0 was used to predict the target of miRNAs. Luciferase assay was used to confirm the predicted results from CircInteractome and starBase v2.0.Results: Expression of circ_0005909 was upregulated in both OS tissues and cell lines. The predicted results from CircInteractome and starBase v2.0 demonstrated that circ_0005909 could sponge miR-338-3p and that HGMA1 was the direct target of miR-338-3p. Cell viability and cell clones was inhibited by knockdown of circ_0005909 but increased by dual inhibition of circ_0005909 and miR-338-3p. Phosphorylation of ERK, Akt, PI3K was inhibited by sh-circ_0005909 while this inhibition was repressed by co-transfection of sh-circ_0005909 and HGMA1.Conclusion: Expression of circ_0005909 was upregulated in both OS tissues and cell lines which upregulated expression of HGMA1 through sponging miR-338-3p, resulting in the activation of MAPK-ERK and PI3K-Akt signaling pathways to promote the development of OS.

HNRNPU-AS1 regulates cell proliferation and apoptosis via miR-205-5p/AXIN2 axis and Wnt/β-catenin signaling pathway in cervical cancer

2021 ◽  
Author(s):  
Zhaoyuan Niu ◽  
Fengling Wang ◽  
Shihui Lv ◽  
Yingpin Lv ◽  
Ming Liu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Underlying Mechanism ◽  
Luciferase Assay ◽  
Flow Cytometry Analysis ◽  
Kaplan Meier ◽  
Dismal Prognosis ◽  
Proliferation And Apoptosis ◽  
Non Coding Rnas ◽  
Expression Loss

Long non-coding RNAs (lncRNAs) have key functions in modulating cervical cancer (CC) genesis and progression. This work focused on exploring lncRNA HNRNPU-AS1's function in CC and the underlying mechanism. HNRNPU-AS1, AXIN2 and miR-205-5p levels in CC cases were measured through RT-qPCR. Relationship between miR-205-5p and AXIN2 or HNRNPU-AS1 was validated through dual-luciferase assay. Cell proliferation was examined by CCK-8, while cell apoptosis by colony formation and flow cytometry analysis. HNRNPU-AS1 expression loss could be observed in CC patients and cell lines, which predicted the dismal prognosis of CC cases. Moreover, it was identified that the miR-205-5p level was up-regulated, which acted as an inhibitory target of HNRNPU-AS1 and AXIN2. HNRNPU-AS1 inhibited cell proliferation and promoted apoptosis. As revealed by Kaplan-Meier curve, CC cases showing low HNRNPU-AS1, high miR-205-5p, and low AXIN2 levels had the poorest prognosis. AXIN2 reversed the CC cell proliferation-promoting, apoptosis-inhibiting and Wnt/β-catenin signaling-activating mediated by miR-205-5p or HNRNPU-AS1 knockout. In conclusion, the overexpression of lncRNA HNRNPU-AS1 suppressed CC progression by inhibiting Wnt/β-catenin pathway through miR-205-5p/AXIN2 axis.

scholarly journals METTL3 promotes lung adenocarcinoma tumor growth and inhibits ferroptosis by stabilizing SLC7A11 m6A modification

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Yiming Xu ◽  
Dandan Lv ◽  
Chao Yan ◽  
Hua Su ◽  
Xue Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Rna Stability ◽  
Underlying Mechanism ◽  
Rna Immunoprecipitation ◽  
Direct Target ◽  
Novel Target

Abstract Background N6-methyladenosine (m6A) has emerged as a significant regulator of the progress of various cancers. However, its role in lung adenocarcinoma (LUAD) remains unclear. Here, we explored the biological function and underlying mechanism of methyltransferase-like 3 (METTL3), the main catalyst of m6A, in LUAD progression. Methods The expression of m6A, METTL3, YTHDF1 and SLC7A11 were detected by immunochemistry or/and online datasets in LUAD patients. The effects of METTL3 on LUAD cell proliferation, apoptosis and ferroptosis were assessed through in vitro loss-and gain-of-function experiments. The in vivo effect on tumorigenesis of METTL3 was evaluated using the LUAD cell xenograft mouse model. MeRIP-seq, RNA immunoprecipitation and RNA stability assay were conducted to explore the molecular mechanism of METTL3 in LUAD. Results The results showed that the m6A level, as well as the methylase METTL3 were both significantly elevated in LUAD patients and lung cancer cells. Functionally, we found that METTL3 could promote proliferation and inhibit ferroptosis in different LUAD cell models, while METTL3 knockdown suppressed LUAD growth in cell-derived xenografts. Mechanistically, solute carrier 7A11 (SLC7A11), the subunit of system Xc−, was identified as the direct target of METTL3 by mRNA-seq and MeRIP-seq. METTL3-mediated m6A modification could stabilize SLC7A11 mRNA and promote its translation, thus promoting LUAD cell proliferation and inhibiting cell ferroptosis, a novel form of programmed cell death. Additionally, we demonstrated that YTHDF1, a m6A reader, was recruited by METTL3 to enhance SLC7A11 m6A modification. Moreover, the expression of YTHDF1 and SLC7A11 were positively correlated with METTL3 and m6A in LUAD tissues. Conclusions These findings reinforced the oncogenic role of METTL3 in LUAD progression and revealed its underlying correlation with cancer cell ferroptosis; these findings also indicate that METTL3 is a promising novel target in LUAD diagnosis and therapy.

scholarly journals MiR-212-3p functions as a tumor suppressor gene in group 3 medulloblastoma via targeting Nuclear Factor I/B (NFIB)

2021 ◽  
Author(s):  
Naveenkumar Perumal ◽  
Ranjana K. Kanchan ◽  
David Doss ◽  
Noah Bastola ◽  
Pranita Atri ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cell ◽  
Colony Formation ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Stem Cell Markers ◽  
Cancer Cell Proliferation ◽  
Group 3

ABSTRACTBackgroundMedulloblastoma (MB), the most frequent malignant pediatric brain tumor, is subdivided into four primary subgroups, wingless-type (WNT), sonic hedgehog (SHH), group 3, and group 4. Haploinsufficiency of chromosome 17p13.3 and c-Myc amplification distinguish high-risk group 3 tumors associated with rapid metastasis, recurrence and early mortality. We sought to identify the role of miR-212-3p, which resides on chromosome 17p13.3, in the pathophysiology of group 3 MB.MethodsWe first determined miR-212-3p expression in group 3 MB using several publicly-available datasets with confirmatory studies in vitro. We then identified epigenetic regulation by studying methylation and HDAC modifications along the promoter region. We used two systems for expression restoration, i.e. transient transfection or stable induction, to delineate miR-212-3p’s tumor suppressive and biochemical properties via assays assessing cancer proliferation, migration, invasion, colony formation, along with cell cycle and apoptosis analyses. We then compared MB and miR target databases to isolate a putative target whose biochemical and oncogenic properties were similarly elucidated using either transient silencing of target expression or stable induction of miR-212-3p.ResultsRNA expression analyses revealed dramatically reduced miR-212-3p levels in group 3 tumors and cell lines mainly through epigenetic silencing via histone modifications. Restoring miR-212-3p expression reduced in vitro cancer cell proliferation, migration, colony formation, and wound healing. Elevated miR-212-3p levels shifted c-Myc phosphorylation (from serine-62 to threonine-58), triggering destabilization and degradation; concurrently, its pro-apoptotic binding partners, i.e., Bin-1 and P19ARF, were upregulated with subsequent elevated apoptotic signals. Using a combination of transcriptomic data and dual luciferase assay, we isolated an oncogenic target of miR-212-3p, i.e. NFIB, a nuclear transcription factor implicated in metastasis and recurrence in various cancers. Increased expression of NFIB was confirmed in group 3 tumors, with poor survival shown in high-expressing patients. Transient NFIB silencing in vitro reduced cancer cell proliferation, colony formation, migration, and invasion. Concurrently, in group 3 MB cells, reduced medullosphere formation along with decreased expression of stem cell markers (Nanog, Oct4, Sox2, CD133) were noted.ConclusionThese results substantiate the tumor-suppressive role of miR-212-3p in group 3 MB and provide a potential therapeutic oncogenic target implicated in metastasis and tumor recurrence.

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