Long Noncoding RNA ANRIL Promotes Cervical Cancer Development by Acting as a Sponge of miR-186

Cervical cancer is a common malignancy of the female reproductive system. Long noncoding RNAs (lncRNAs) have been reported to modulate tumor progression in multiple cancers. The lncRNA antisense noncoding RNA in the INK4 locus (ANRIL) has been identified as an oncogenic molecular target in several tumors; however, the function and underlying mechanism involved in cervical cancer oncogenesis are still unclear. In the present study, RT-PCR showed that ANRIL expression was significantly upregulated in cervical cancer tumors and cell lines. Nevertheless, ANRIL knockdown transfected with interference oligonucleotide inhibited the proliferation activity and invasive ability, and promoted apoptosis of cervical cancer cell lines. The bioinformatics prediction program and luciferase assay predicted and validated that miR-186 directly targeted ANRIL. The expression level of miR-186 was downregulated in cervical cancer tumors and cell lines and was negatively correlated to that of ANRIL. Moreover, rescue experiments showed that miR-186 inhibitor could reverse the suppression of ANRIL knockdown. In summary, our study demonstrated that the ANRIL/miR-186 axis might play a vital role in cervical cancer tumorigenesis.

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Long Noncoding RNA HOTAIR: An Oncogene in Human Cervical Cancer Interacting With MicroRNA-17-5p

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504017x15002869385155 ◽

2018 ◽

Vol 26 (3) ◽

pp. 353-361 ◽

Cited By ~ 15

Author(s):

Fei Ji ◽

Delinaer Wuerkenbieke ◽

Yan He ◽

Yan Ding ◽

Rong Du

Keyword(s):

Cervical Cancer ◽

Cell Lines ◽

Noncoding Rna ◽

Underlying Mechanism ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Loss Of Function ◽

Cervical Cells ◽

Cervical Cancer Development ◽

Cancer Tissues

Increasing evidence has indicated that long noncoding RNAs (lncRNAs) are a class of significant regulators in various tumorigenesis processes. The lncRNA homeobox transcript antisense RNA (HOTAIR) has been reported to act as a functional lncRNA in cervical cancer development. The present study investigated the underlying mechanism of HOTAIR and miR-17-5p in cervical cancer tumorigenesis. The results showed that HOTAIR expression was significantly upregulated in both cervical cancer tissues and cell lines. Loss-of-function experiments showed that HOTAIR knockdown inhibited the proliferation, migration, and invasion of cervical cells. In addition, miR-17-5p expression was downregulated in cervical cancer tissues and cell lines. Pearson’s correlation analysis indicated that miR-17-5p expression was negatively correlated to that of HOTAIR. Luciferase reporter assay revealed that miR-17-5p directly targeted HOTAIR 3′-UTR. Rescue experiments showed that miR-17-5p knockdown could reverse the tumor-suppressing effect caused by si-HOTAIR transfection. In summary, our results reveal the tumor-promoting role of HOTAIR in cervical cancer via sponging miR-17-5p, providing a novel therapeutic target for future treatment of cervical cancer.

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LncRNA BANCR Promotes Pancreatic Cancer Tumorigenesis via Modulating MiR-195-5p/Wnt/β-Catenin Signaling Pathway

Technology in Cancer Research & Treatment ◽

10.1177/1533033819887962 ◽

2019 ◽

Vol 18 ◽

pp. 153303381988796 ◽

Cited By ~ 6

Author(s):

Xinquan Wu ◽

Tianfang Xia ◽

Meng Cao ◽

Pengbo Zhang ◽

Guodong Shi ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cell Lines ◽

Noncoding Rna ◽

Underlying Mechanism ◽

Vital Role ◽

Luciferase Reporter ◽

Carcinogenic Activity ◽

Invasion And Migration ◽

Sw1990 Cell

Long noncoding BRAF-activated noncoding RNA has been reported to be tightly associated with tumorigenesis and development in various types of cancers. However, the expression, biological function, and modulatory mechanism of BRAF-activated noncoding RNA in pancreatic cancer remained unclear. In the present work, we explored the carcinogenic activity and underlying mechanism of BRAF-activated noncoding RNA on pancreatic cancer in vitro. We identified that BRAF-activated noncoding RNA was upregulated in pancreatic cancer tissues and cell lines, and BRAF-activated noncoding RNA was related to tumor metastasis and stage. BRAF-activated noncoding RNA reinforces proliferation, invasion, and migration in PANC-1 and SW1990 cells. Moreover, miR-195-5p was downregulated in both PC tissues and cell lines. Our results based on luciferase reporter, RIP-Ago2 and qRT-PCR assays, showed that miR-195-5p was a direct target of BRAF-activated noncoding RNA. Furthermore, miR-195-5p inhibitor abrogated the effects of short-interfering BRAF-activated noncoding RNA on PANC-1 and SW1990 cell growth and invasion in vitro. We further identified that BRAF-activated noncoding RNA played a vital role in activating the Wnt/β-catenin pathway by sponging miR-195-5p. Collectively, our study showed that BRAF-activated noncoding RNA promotes pancreatic cancer tumorigenesis through miR-195-5p/Wnt/β-catenin axis may serve as a potential target for diagnostics and therapeutics in pancreatic cancer.

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MiR-195 Suppresses Cervical Cancer Migration and Invasion Through Targeting Smad3

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000686 ◽

2016 ◽

Vol 26 (5) ◽

pp. 817-824 ◽

Cited By ~ 30

Author(s):

Quan Zhou ◽

Ling R. Han ◽

Yang X. Zhou ◽

Yan Li

Keyword(s):

Cervical Cancer ◽

Cell Lines ◽

Cancer Metastasis ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Gynecology And Obstetrics ◽

Clinicopathological Significance ◽

Cervical Cancer Development ◽

Cancer Tissues

ObjectiveMicroRNAs (miRNAs) play crucial roles in cervical cancer development and progression. The purposes of this study were to investigate the role of miR-195 in cervical cancer and clarify the regulation of Smad3 by miR-195.MethodsQuantitative real-time polymerase chain reaction was used to examine miR-195 expression in cervical cancer tissues and cell lines. The clinicopathological significance of miR-195 down-regulation was further analyzed. Transwell migration and invasion assays were performed. A luciferase reporter assay was conducted to confirm the target gene of miR-195, and the results were validated in cervical cancer tissues and cell lines.ResultsMiR-195 was significantly decreased in clinical tissues and cervical cancer cell lines. The low miR-195 level was significantly correlated with higher International Federation of Gynecology and Obstetrics stage, node metastasis, and deep stromal invasion. Up-regulation of miR-195 suppressed cell migration and invasion in vitro. Smad3 was verified as a direct target of miR-195, which was further confirmed by the inverse expression of miR-195 and Smad3 in patients’ specimens.ConclusionsThe newly identified miR-195/Smad3 pathway provides an insight into cervical cancer metastasis and may represent a novel therapeutic target.

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LncRNA DANCR functions as a competing endogenous RNA to regulate RAB1A expression by sponging miR-634 in glioma

Bioscience Reports ◽

10.1042/bsr20171664 ◽

2018 ◽

Vol 38 (1) ◽

Cited By ~ 25

Author(s):

Dawei Xu ◽

Jian Yu ◽

Guojun Gao ◽

Guangjian Lu ◽

Yi Zhang ◽

...

Keyword(s):

Cell Lines ◽

Noncoding Rna ◽

Molecular Mechanisms ◽

Glioma Cells ◽

Tumor Grade ◽

Underlying Mechanism ◽

Luciferase Reporter ◽

Biological Functions ◽

Advanced Tumor ◽

Rna Immunoprecipitation

Long noncoding RNA (lncRNA) differentiation antagonizing nonprotein coding RNA (DANCR) plays important regulatory roles in many solid tumors. However, the effect of DANCR in glioma progression and underlying molecular mechanisms were not entirely explored. In the present study, we determined the expression of DANCR in glioma tissues and cell lines using qRT-PCR and further defined the biological functions. Furthermore, we used luciferase reporter assay, Western blot, and RNA immunoprecipitation (RIP) to explore the underlying mechanism. Our results showed that DANCR was significantly up-regulated in glioma tissues and cell lines (U251, U118, LN229, and U87MG). High DANCR expression was correlated with advanced tumor grade. Inhibition of DANCR suppressed the glioma cells proliferation and induced cells arrested in the G0/G1 phase. In addition, we verified that DANCR could directly interact with miR-634 in glioma cells and this interaction resulted in the inhibition of downstream of RAB1A expression. The present study demonstrated that DANCR/miR-634/RAB1A axis plays crucial roles in the progression of glioma, and DANCR might potentially serve as a therapeutic target for the treatment of glioma patients.

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Long noncoding RNA CASC2 suppresses esophageal squamous cell carcinoma progression by increasing SOCS1 expression

Cell & Bioscience ◽

10.1186/s13578-019-0353-4 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Ke Sun ◽

Guangping Zhang

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Noncoding Rna ◽

Cancer Susceptibility ◽

Underlying Mechanism ◽

Luciferase Assay ◽

Migration And Invasion ◽

Cytokine Signaling

Abstract Objective Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer-related deaths worldwide. Emerging evidence suggests the involvement of long noncoding RNAs (lncRNAs) in tumorigenesis. LncRNA Cancer Susceptibility Candidate 2 (CASC2) has been demonstrated to act as a tumor suppressor contributing to the development and progression of several cancers. However, the functional significance and underlying mechanism of CASC2 in ESCC progression has not been well elucidated. Methods The expression levels of CASC2 in ESCC tissues were detected by qRT-PCR. CASC2 overexpression and knockdown models were established and used to investigate the functional role of CASC2 in ESCC cells. RIP, RNA pull-down and dual-luciferase assay was used to detect the association between CASC2 and miR-155. The interaction between CASC2 and Suppressor Of Cytokine Signaling 1 (SOCS1) was assessed by RIP and RNA pull-down assays. Results In the present study, we found that CASC2 was significantly downregulated in ESCC tissues and positively correlated with overall survival time of patients with ESCC. Functional assays demonstrated that CASC2 suppressed proliferation, migration and invasion, as well as enhanced drug sensitivity in ESCC cells. Mechanistically, CASC2 inhibited ESCC progression by upregulating the expression of SOCS1 via two different ways. CASC2 acted as competing endogenous RNA (ceRNA) for miR-155 to post-transcriptionally increase SOCS1 expression. On the other hand, CASC2 was capable of interacting with SOCS1 protein and suppressing its degradation. Conclusion Conclusively, these results demonstrated that CASC2 could exert as a tumor suppressive lncRNA in ESCC progression via regulating SOCS1.

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Long Noncoding RNA MALAT1 Interacts with miR-124-3p to Modulate Osteosarcoma Progression by Targeting SphK1

Journal of Oncology ◽

10.1155/2021/8390165 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Bin Liu ◽

Xinli Zhan ◽

Chong Liu

Keyword(s):

Cell Proliferation ◽

Cell Lines ◽

Noncoding Rna ◽

Underlying Mechanism ◽

Luciferase Reporter ◽

Cell Proliferation And Migration ◽

Lncrna Malat1 ◽

And Migration ◽

Tissue Specimens ◽

Proliferation And Migration

Introduction. Long noncoding RNAs (lncRNAs) have been implicated in a variety of biological functions, including tumor proliferation, apoptosis, progression, and metastasis. lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is overexpressed in various cancers, as well as osteosarcoma (OS); however, its underlying mechanism in OS is poorly understood. This investigation aims to elucidate the mechanisms of MALAT1 in OS proliferation and migration and to provide theoretical grounding for further targeted therapy in OS. Methods. In the present study, we applied qRT-PCR to assess the MALAT1 expression in OS tissues and cell lines. The effects of MALAT1 and miR-124-3p on OS cell proliferation and migration were studied by CCK-8 and scratch assays. Cell cycle and apoptosis were tested using a flow cytometer. The competing relationship between MALAT1 and miR-124-3p was confirmed by dual-luciferase reporter assay. Results. MALAT1 was overexpressed in OS cell lines and tissue specimens, and knockdown of MALAT1 significantly inhibited cell proliferation and migration and increased cell apoptosis and the percentage of G0/G1 phase. Furthermore, MALAT1 could directly bind to miR-124-3p and inhibit miR-124-3p expression. Moreover, MALAT1 overexpression significantly relieved the inhibition on OS cell proliferation mediated by miR-124-3p overexpression, which involved the derepression of sphingosine kinase 1 (SphK1). Conclusions. We propose that lncRNA MALAT1 interacts with miR-124-3p to modulate OS progression by targeting SphK1. Hence, we identified a novel MALAT1/miR-124-3p/SphK1 signaling pathway in the regulation of OS biological behaviors.

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

Cell Transplantation ◽

10.1177/0963689719861063 ◽

2019 ◽

Vol 28 (9-10) ◽

pp. 1299-1305 ◽

Cited By ~ 7

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.

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LncRNA JPX promotes cervical cancer progression by modulating miR-25-3p/SOX4 axis

Cancer Cell International ◽

10.1186/s12935-020-01486-3 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Xia Chen ◽

Jingxiu Yang ◽

Yuping Wang

Keyword(s):

Cervical Cancer ◽

Cell Lines ◽

Cancer Progression ◽

Hela Cells ◽

Noncoding Rna ◽

Tumor Development ◽

Tumor Xenograft ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Aberrant Expression

Abstract Background The long noncoding RNA (lncRNA) JPX is a molecular switch for X-chromosome inactivation. Accumulating studies have shown that the aberrant expression and function of lncRNAs are involved in the occurrence and development of tumors. However, the functional importance and mechanism of the action of lncRNA JPX in cervical cancer (CC) remain unknown. Method In this study, qRT-PCR and western blotting were used to evaluate the mRNA or protein expression of JPX, miR-25-3p and SOX4 in CC tissues and cell lines. StarBase v2.0 database, luciferase reporter assay and RNA immunoprecipitation assay were used to explore the relationship between JPX and miR-25-3p. EdU assay, CCK-8 assay and transwell assay were utilized to evaluate the proliferation, migration and invasion of CC cells. The tumor xenograft assay in nude mice was performed to demonstrate the role of the JPX/miR-25-3p/SOX4 axis in CC. Results We found that JPX was markedly upregulated, whereas miR-25-3p was markedly downregulated in CC tissues and cell lines, and the expression of JPX was negatively correlated with miR-25-3p in CC tissues. Moreover, overexpression of JPX increased proliferation, migration and invasion of HeLa cells, whereas knockdown of JPX decreased proliferation, migration and invasion of HeLa cells. In contrast to JPX, overexpression of miR-25-3p decreased proliferation, migration and invasion of HeLa cells. In addition, knockdown of JPX was found to inhibit HeLa cell viability and tumor development via up-regulating the expression of miR-25-3p and inhibiting the expression of SOX4. Conclusions Our study demonstrates that JPX promotes cervical cancer progression through modulating the miR-25-3p/SOX4 axis, and may serve as a potential target for CC therapy.

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Long Noncoding RNA LINC00460 Facilitates the Proliferation and Metastasis of Renal Cell Carcinoma via PI3K/AKT Signaling Pathway

10.21203/rs.3.rs-483043/v1 ◽

2021 ◽

Author(s):

Feng-Juan Zhou ◽

Sen Meng ◽

Hongmei Yong ◽

Ping-Fu Hou ◽

Min-Le Li ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Cell Lines ◽

Renal Cell ◽

Noncoding Rna ◽

Underlying Mechanism ◽

The Cancer Genome Atlas ◽

Akt Pathway

Abstract Renal cell carcinoma (RCC) is one of the most prevalent cancers. Long noncoding RNAs (LncRNAs) have been indicated as a mediator acted in tumorigenesis of RCC. However, the mechanism of LINC00460 on RCC is yet to be investigated. This study aimed to investigate the potential function of LINC00460 and underlying mechanism of RCC. We detected LINC00460 expression in RCC tissues and the prognosis in RCC patients using Gene Expression Profiling Interactive Analysis (GEPIA) website and The Cancer Genome Atlas (TCGA) database. LINC00460 level in normal renal cell line and RCC cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). We study the effects of LINC00460 on proliferation, migration, invasion, apoptosis in RCC cells lines using a series of in vivo and in vitro experiments. RNA sequencing (RNA-seq) analysis for the whole transcriptome was applied to searching potential LINC00460 related signal pathway in RCC. We identified the significant up-regulated expression level of LINC00460 in RCC tissues and cell lines. Elevated LINC00460 was correlated with shorter survival of RCC patients. Overexpression of LINC00460 promoted cell viability, proliferation, invasion and migration, while down-regulation of LINC00460 exerted inhibitory effect on these activities. We crucially identified that LNC00460 promotes development of RCC by influencing the PI3K/AKT pathway. Knockdown of LNC00460 decreased the phosphorylation of AKT and mTOR. The key finding of our study provided a new evidence suggesting that LINC00460 functions as an oncogene in RCC pathogenesis by mediating the PI3K/AKT pathway, which may provide a new target for the treatment of RCC.

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