scholarly journals Inhibition of lncRNA-NEAT1 sensitizes 5-Fu resistant cervical cancer cells through de-repressing the microRNA-34a/LDHA axis

2021 ◽  
Author(s):  
Xuecheng Shao ◽  
Xuehui Zheng ◽  
Dan Ma ◽  
Yang Liu ◽  
Guoyan Liu
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cervical Cancer Patient ◽  
Cervical Cancer Cells ◽  
Key Enzyme ◽  
Direct Targeting ◽  
Cancer Tissues ◽  
Lncrna Neat1 ◽  
Competitive Endogenous Rna ◽  
Resistant Cells

Cervical cancer is one of the most diagnosed malignancies among females. The 5-fluorouracil (5-Fu) is a widely used chemotherapeutic agent against diverse cancers. Despite the initially encouraging progresses, a fraction of cervical cancer patients developed 5-Fu resistance. We detected that NEAT1 was significantly upregulated in cervical cancer tissues and cell lines. Moreover, NEAT1 was positively associated with 5-Fu resistance. Furthermore, expression of NEAT1 was significantly upregulated in 5-Fu resistant CaSki cervical cancer cells. Knocking down NEAT1 by shRNA dramatically promoted the sensitivity of 5-Fu resistant CaSki cells. We observed a negative correlation between lncRNA-NEAT1 and miR-34a in cervical cancer patient tissues. Overexpression of miR-34a significantly sensitized 5-Fu resistant cells. Bioinformatical analysis uncovered that NEAT1 functions as a competitive endogenous RNA (ceRNA) of miR-34a in cervical cancer cells via sponging it at multiple sites to suppress expression of miR-34a. This negative association between NEAT1 and miR-34a was further verified in cervical cancer tissues. We found the 5-Fu resistant cells displayed significantly increased glycolysis rate. Overexpression of miR-34a suppressed cellular glycolysis rate and sensitized 5-Fu resistant cells through direct targeting the 3’UTR of LDHA, a glycolysis key enzyme. Importantly, knocking down NEAT1 successfully downregulated LDHA expressions and glycolysis rate of cervical cancer cells by upregulating miR-34a, a process could be further rescued by miR-34a inhibition. Finally, we demonstrated inhibition of NEAT1 significantly sensitized cervical cancer cells to 5-Fu through the miR-34a/LDHA pathway. In summary, this study suggests a new molecular mechanism for the NEAT1-mediated 5-Fu resistance via the miR-34a/LDHA-glycolysis axis

scholarly journals lncRNA DLG1-AS1 Promotes Cell Proliferation by Competitively Binding with miR-107 and Up-Regulating ZHX1 Expression in Cervical Cancer

2018 ◽  
Vol 49 (5) ◽  
pp. 1792-1803 ◽  
Author(s):  
Xiaohui Rui ◽  
Yun Xu ◽  
Yaqing Huang ◽  
Linjuan Ji ◽  
Xiping Jiang
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Target Genes ◽  
Cell Counting ◽  
Cervical Cancer Cells ◽  
A Cell ◽  
Non Coding Rnas ◽  
Biological Methods ◽  
Cancer Tissues ◽  
Competitive Endogenous Rna

Background/Aims: Recent studies have revealed that long non-coding RNAs (lncRNAs) are involved in the occurrence and development of various tumors, thereby attracting increasing attention from researchers. The important biological functions of lncRNAs have been recognized gradually, but their mechanism in cervical cancer remains unclear. Methods: Differentially expressed lncRNAs in cervical cancer and para-carcinoma tissues were identified by screening using an lncRNA array, and candidate lncRNAs were verified by quantitative real-time PCR. A series of bioinformatics and molecular biological methods were adopted to investigate the interactions among lncRNAs, microRNAs (miRNAs), and miRNA target genes in cervical cancer. Cell viability was measured using a Cell Counting Kit-8 assay. Results: DLG1-AS1 was the most significantly up-regulated lncRNA in cervical cancer tissues, and it was confirmed that cervical cancer patients with high DLG1-AS1 expression had a poor prognosis. Down-regulation of DLG1-AS1 expression suppressed the proliferation of cervical cancer cells. Further investigation revealed that DLG1-AS1 eliminated the inhibition of miR-107 on the expression of its target gene ZHX1 by competitively binding to miR-107. Moreover, rescue assays proved that the effect of DLG1-AS1 on the proliferation of cervical cancer cells was dependent on miR-107. Conclusion: DLG1-AS1/miR-107/ZHX1 can form a competitive endogenous RNA network that regulates the proliferation of cervical cancer cells, resulting in tumor progression.

Long noncoding RNA NEAT1 promotes the growth of cervical cancer cells via sponging miR-9-5p

2019 ◽  
Vol 97 (2) ◽  
pp. 100-108 ◽  
Author(s):  
Qiuxian Xie ◽  
Shanna Lin ◽  
Manjia Zheng ◽  
Qiutao Cai ◽  
Ya Tu
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Noncoding Rna ◽  
Inhibitory Effect ◽  
Micro Rna ◽  
Cancer Cell Growth ◽  
Cervical Cancer Cells ◽  
And Migration ◽  
Cancer Tissues ◽  
Competitive Endogenous Rna

Evidence has accumulated demonstrating that long noncoding RNAs (lncRNAs) participate in the initiation and progression of cancers. In this study, we found that the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) is significantly increased in both cervical cancer tissues and cell lines. Overexpression of NEAT1 promoted the proliferation and migration of cervical cancer cells. Molecular studies uncovered that NEAT1 functions as competitive endogenous RNA (ceRNA), binding the micro-RNA miR-9-5p and suppressing its expression. However, we consistently found that when NEAT1 was highly expressed, it attenuated the inhibitory effect of miR-9-5p on the expression of PTEN and POU2F1, which are the targets of miR-9-5p. Consistent with the negative regulation of NEAT1 on miR-9-5p, restoration of miR-9-5p inhibited the growth-promoting effects of NEAT1 on cervical cancer cells. Taken together, these results indicated that NEAT1 plays an important role in the regulation cervical cancer cell growth by targeting miR-9-5p. Our findings characterized the possible mechanism of NEAT1 in cervical cancer.

scholarly journals MicroRNA-96-5p Facilitates the Viability, Migration, and Invasion and Suppresses the Apoptosis of Cervical Cancer Cells byNegatively Modulating SFRP4

2020 ◽  
Vol 19 ◽  
pp. 153303382093413 ◽  
Author(s):  
Huiling Zhang ◽  
Ruxin Chen ◽  
Jinyan Shao
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Clinical Stage ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Related Protein ◽  
Siha Cells ◽  
Gene Assay ◽  
Cervical Cancer Cells ◽  
Cancer Tissues

Purpose: The current study was intended to research the functional role and regulatory mechanism of microRNA-96-5p in the progression of cervical cancer. Methods: MicroRNA-96-5p expression in cervical cancer tissues was assessed by quantitative real-time polymerase chain reaction. The association between microRNA-96-5p expression and clinicopathological features of patients with cervical cancer was analyzed. MTT, flow cytometry, wound healing, and transwell assay were performed to evaluate the viability, apoptosis, migration, and invasion of Hela and SiHa cells. Targetscan, dual-luciferase reporter gene assay, and RNA pull-down analysis were constructed to evaluate the target relationship between microRNA-96-5p and secreted frizzled-related protein 4. Results: MicroRNA-96-5p was overexpressed in cervical cancer tissues, and microRNA-96-5p expression was markedly associated with the clinical stage and lymph node metastasis of patients with cervical cancer. Overexpressed microRNA-96-5p facilitated the viability, migration, invasion, and inhibited the apoptosis of Hela and SiHa cells, whereas suppression of microRNA-96-5p exerted the opposite trend. Secreted frizzled-related protein 4 was proved to be a target of microRNA-96-5p. Silencing of secreted frizzled-related protein 4 eliminated the anti-tumor effect of microRNA-96-5p on cervical cancer cells. Conclusions: MicroRNA-96-5p facilitated the viability, migration, and invasion and inhibited the apoptosis of cervical cancer cells via negatively regulating secreted frizzled-related protein 4.

scholarly journals RNA-sequencing identified miR-3681 as a negative regulator in the proliferation and migration of cervical cancer cells via the posttranscriptional suppression of HGFR

RSC Advances ◽  
2019 ◽  
Vol 9 (39) ◽  
pp. 22376-22383 ◽  
Author(s):  
Fan Shi ◽  
Yingbing Zhang ◽  
Juan Wang ◽  
Jin Su ◽  
Zi Liu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Rna Sequencing ◽  
Negative Regulator ◽  
Tumor Tissues ◽  
Differentially Expressed Mirnas ◽  
Cervical Cancer Cells ◽  
And Migration ◽  
Cancer Tissues ◽  
Proliferation And Migration

In this study, RNA-sequencing was used to investigate the differentially expressed miRNAs between cervical cancer tissues and matched adjacent non-tumor tissues.

scholarly journals Upregulation of Long Non-Coding RNA Small Nucleolar RNA Host Gene 12 Contributes to Cell Growth and Invasion in Cervical Cancer by Acting as a Sponge for MiR-424-5p

2018 ◽  
Vol 45 (5) ◽  
pp. 2086-2094 ◽  
Author(s):  
Jing Dong ◽  
Qing Wang ◽  
Li Li ◽  
Zhang Xiao-jin
Keyword(s):  
Cervical Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Host Gene ◽  
Migration And Invasion ◽  
Small Nucleolar Rna ◽  
Cervical Cancer Cells ◽  
Cancer Tissues ◽  
Nucleolar Rna

Background/Aims: Cervical cancer, which is one of the most aggressive cancers affecting females, has high rates of recurrence and mortality. Small nucleolar RNA host gene 12 (SNHG12) is known to promote the progression of several cancers; however, its exact effects and molecular mechanisms in cervical cancer remain unknown. Methods: Real-time quantitative PCR was used to determine the expression level of SNHG12 in cervical cancer tissues and cell lines. Loss-of-function assays were performed to examine the effect of SNHG12 on the proliferation, apoptosis, migration and invasion of cervical cancer cells in vitro and tumor growth in vivo. Luciferase experiments were employed to explore the interactions between SNHG12 and miR-424-5p. Results: SNHG12 was found to be abnormally elevated in human cervical cancer tissues compared with paired adjacent normal tissues. Moreover, high SNHG12 expression in tumor tissues was significantly correlated with vascular involvement, lymph node metastasis, advanced FIGO stage and poor prognosis. Furthermore, the knockdown of SNHG12 was found to inhibit proliferation, migration and invasion of cervical cancer cells in vitro, and silencing SNHG12 was shown to suppress tumor growth in a nude mouse model. Mechanistic studies showed that SNHG12 functioned as an endogenous sponge for miR-424-5p, thereby downregulating the expression of miR-424-5p in cervical cancer. Furthermore, the inhibition of miR-424-5p in SNHG12-depleted cells partially reversed the effects on cervical cancer cell apoptosis, adhesion and invasion. Conclusion: In summary, our findings suggest that the tumor-promoting role of SNHG12 is to function as a molecular sponge, which negatively regulates miR-424-5p. These findings may provide a potent therapeutic target for cervical cancer.

scholarly journals Overexpression of miR-142-5p suppresses the progression of cervical cancer through targeting PIK3AP1 expression

2020 ◽  
Author(s):  
Junliang Guo ◽  
Tian Tang ◽  
Jinhong Li ◽  
Yihong Yang ◽  
Yi Quan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Gain Function ◽  
Cervical Cancer Cells ◽  
Target Binding ◽  
Cancer Tissues

The aim of current study was to explore the mechanism of miR-142-5p in cervical cancer through mediating the PIK3AP1/P13K/AKT axis. To this end, RT-qPCR and Western blot analysis results revealed that miR-142-5p was poorly expressed, whereas PIK3AP1 was highly expressed in cervical cancer tissues and cells. Furthermore, miR-142-5p was hypermethylated in cervical cancer, as reflected by MS-PCR and ChIP assessment of enrichment of DNMT1/DNMT3a/DNMT3b in the promoter region of miR-142-5p. A target binding relationship between miR-142-5p and PIK3AP1 was established, showing that miR-142-5p targeted and inhibited the expression of PIK3AP1. Loss- and gain- function assays were conducted to determine the roles of miR-142-5p and PIK3AP1 in cervical cancer cells. CCK-8, flow cytometry and Transwell assay results revealed that overexpression of miR-142-5p in cervical cancer cells downregulated PIK3AP1 and inhibited the P13K/AKT signaling pathway, leading to reduced proliferation, migration, and invasion capacity of cervical cancer cells, but enhanced apoptosis. Collectively, epigenetic regulation of miR-142-5p targeted PIK3AP1 to inactivate the P13K/AKT signaling pathway, thus suppressing development of cervical cancer, which presents new targets for the treatment of cervical cancer.

scholarly journals Up-regulation of peroxiredoxin 3 by high-risk human papillomavirus in cervical cancer cells

2021 ◽  
Author(s):  
Hou-Li Liu ◽  
Xiao-Juan Sun ◽  
Xiaoyan Li ◽  
Jingmin Li ◽  
Xianyong Bai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cervical Cancer ◽  
Human Papillomavirus ◽  
High Risk ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cervical Cancer Cells ◽  
Cancer Tissues ◽  
High Risk Hpv ◽  
Peroxiredoxin 3

IntroductionPeroxiredoxin 3 (PRX3) is a member of PRX family with antioxidant functions by scavenging hydrogen peroxide. Since the development of cervical cancer is causally linked to high-risk human papillomavirus (HPV) that induces oxidative stress, we conducted the present study to investigate the response of PRX3 to high-risk HPV infection.Material and methodsThis study included fifty-six patients with invasive squamous cervical cancer and sixty control patients with hysteromyoma. Enzyme-linked immunosorbent assay was performed to detect cervical oxidative stress and serum PRX3. The expression of PRX3 and oncoprotein E6 of HPV16 or HPV18 was examined in cervical cancer tissues by immunohistochemistry. Western Blot was applied to detect the expression of PRX3 and E6 in cervical cancer cell lines including CaSki, HeLa, and C33A.ResultsPatients with cervical cancer showed higher serum PRX3 than control patients with hysteromyoma. Levels of oxidative markers in cervical cancer tissues were elevated as compared to normal cervical epithelia. PRX3 expression was upregulated in cervical cancer tissues and the upregulation was positively associated with the expression of E6 of HPV16 or HPV18. The association was confirmed in HPV-containing cervical cancer cell lines including CaSki and HeLa.ConclusionsOur results indicated a positive response of PRX3 to HPV-induced oxidative stress. Serum PRX3 might be a potential indicator of active amplification of high-risk HPV in cervical cancer cells.

scholarly journals TM7SF2 regulates cell proliferation and apoptosis by activation of C-Raf/ERK pathway in cervical cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yichi Xu ◽  
Xin Chen ◽  
Shuya Pan ◽  
Zhi-wei Wang ◽  
Xueqiong Zhu
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cholesterol Metabolism ◽  
Vital Role ◽  
Erk Pathway ◽  
Tumorigenesis And Progression ◽  
Cervical Cancer Cells ◽  
Cancer Tissues

AbstractTransmembrane 7 superfamily member 2 (TM7SF2) coding an enzyme involved in cholesterol metabolism has been found to be differentially expressed in kinds of tissues. Nevertheless, the role of TM7SF2 in the regulation of growth and progression among various cancers is unclear. In this study, the immunohistochemistry (IHC) assay, real-time RT-PCR and western blotting analysis were used to determine the TM7SF2 expression in cervical cancer tissues. Next, we used multiple methods to determine the ability of cell proliferation, migration, invasion, apoptosis, and cell cycle in cervical cancer cells after TM7SF2 modulation, such as CCK8 assay, colony formation assay, Transwell assay, wound healing assay, and flow cytometry. Our results revealed that upregulation of TM7SF2 facilitated cell proliferation and metastasis, suppressed cell apoptosis and prevented G0/G1 phase arrests in C33A and SiHa cells. Consistently, the opposite effects were observed after TM7SF2 knockout in cervical cancer cells. Further, we found that TM7SF2 participated in promoting tumorigenesis and progression via activation of C-Raf/ERK pathway in cervical cancer, which can be partly reversed by Raf inhibitor LY3009120. Moreover, TM7SF2 overexpression contributed to enhancement of xenograft tumor growth in vivo. Our findings indicated that TM7SF2 plays a vital role in tumor promotion by involving in C-Raf/ERK activation. Therefore, TM7SF2 could serve as a therapeutic target in future cervical cancer treatment.

Sevoflurane Inhibits Growth and Metastasis of Cervical Cancer Through Up-Regulating miR-203 by Targeting Tumor Protein Translationally Controlled 1

2020 ◽  
Vol 10 (6) ◽  
pp. 874-883
Author(s):  
Li Zhang ◽  
Shiyou Wei ◽  
Zhenkai Xu ◽  
Wen Sun ◽  
Lihua Hang
Keyword(s):  
Cervical Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Target Genes ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Reporter System ◽  
Cervical Cancer Cells ◽  
Induced Apoptosis ◽  
Cancer Tissues

Background: Cervical cancer is a type of malignancy with high incidence and high mortality in women all over the world. Recent findings revealed the role of sevoflurane in the inhibition of development of various cancer types. This study aimed to explore whether sevoflurane could suppress cells proliferation and metastasis through adjusting miR-203 expression in cervical cancer. Methods: The effects of sevoflurane on HeLa cell viability was assessed using CCK-8 assay. miR-203 level in Hela cells was determined by qRT-PCR. In addition, cells apoptosis, migration and invasion were evaluated using flow cytometry and transwell analysis respectively after sevoflurane treatment or miR-203 expression changes. Bioinformatics software (TargetScan) was used to predict the potential target genes for miR-203 and the prediction was validated using dual-luciferase reporter system. Results: Sevoflurane effectively inhibited cell viability, metastasis and stimulated apoptosis in cervical cancer. miR-203 demonstrated a low expression in cervical cancer tissues and cells and sevoflurane significantly up-regulated miR-203 expression in cervical cancer cells. Upregulation of miR-203 significantly suppressed cell growth and metastasis and induced apoptosis, while down-regulation of miR-203 presented the opposite effects in cervical cancer cells. In addition, the inhibitory effects of sevoflurane were eliminated by down-regulating miR-203 in cervical cancer cells. In addition, TPT1 was confirmed as a target gene for miR-203. Conclusion: Sevoflurane inhibited cervical cancer cells viability and metastasis through up-regulation of miR-203 expression by targeting TPT1.

Sign in / Sign up

Export Citation Format

Share Document