scholarly journals KCNQ1OT1: An Oncogenic Long Noncoding RNA

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1602
Author(s):  
Patrice Cagle ◽  
Qi Qi ◽  
Suryakant Niture ◽  
Deepak Kumar
Keyword(s):  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Vital Role ◽  
Migration And Invasion ◽  
Biological Functions ◽  
Aberrant Expression ◽  
Human Cancers ◽  
Oral Melanoma ◽  
Opposite Strand

Long noncoding RNAs (lncRNAs) are transcripts greater than 200 nucleotides that do not code for proteins but regulate gene expression. Recent studies indicate that lncRNAs are involved in the modulation of biological functions in human disease. KCNQ1 Opposite Strand/Antisense Transcript 1 (KCNQ1OT1) encodes a lncRNA from the opposite strand of KCNQ1 in the CDKN1C/KCNQ1OT1 cluster that is reported to play a vital role in the development and progression of cancer. KCNQ1OT1 regulates cancer cell proliferation, cell cycle, migration and invasion, metastasis, glucose metabolism, and immune evasion. The aberrant expression of KCNQ1OT1 in cancer patients is associated with poor prognosis and decreased survival. This review summarizes recent literature related to the biological functions and molecular mechanisms of KCNQ1OT1 in various human cancers, including colorectal, bladder, breast, oral, melanoma, osteosarcoma, lung, glioma, ovarian, liver, acute myeloid leukemia, prostate, and gastric. We also discuss the role of KCNQ1OT1 as a promising diagnostic biomarker and a novel therapeutic target in human cancers.

scholarly journals Regulatory Role of microRNAs Targeting the Transcription Co-Factor ZNF521 in Normal Tissues and Cancers

2021 ◽  
Vol 22 (16) ◽  
pp. 8461
Author(s):  
Emanuela Chiarella ◽  
Annamaria Aloisio ◽  
Stefania Scicchitano ◽  
Heather Mandy Bond ◽  
Maria Mesuraca
Keyword(s):  
Transcription Factor ◽  
Molecular Mechanisms ◽  
Transitional Cell ◽  
Biological Functions ◽  
Aberrant Expression ◽  
Normal Tissues ◽  
Novel Mirna ◽  
Mirna Expression Profiling ◽  
Mirna Deregulation

Powerful bioinformatics tools have provided a wealth of novel miRNA–transcription factor networks crucial in controlling gene regulation. In this review, we focus on the biological functions of miRNAs targeting ZNF521, explaining the molecular mechanisms by which the dysregulation of this axis contributes to malignancy. ZNF521 is a stem cell-associated co-transcription factor implicated in the regulation of hematopoietic, neural, and mesenchymal stem cells. The aberrant expression of ZNF521 transcripts, frequently associated with miRNA deregulation, has been detected in several tumors including pancreatic, hepatocellular, gastric, bladder transitional cell carcinomas as well as in breast and ovarian cancers. miRNA expression profiling tools are currently identifying a multitude of miRNAs, involved together with oncogenes and TFs in the regulation of oncogenesis, including ZNF521, which may be candidates for diagnostic and prognostic biomarkers of cancer.

scholarly journals Long noncoding RNA CASC2c inhibited cell proliferation in hepatocellular carcinoma by inactivated ERK1/2 and Wnt/β-catenin signaling pathway

2019 ◽  
Vol 22 (3) ◽  
pp. 302-310 ◽  
Author(s):  
Q. Y. Li ◽  
K. Yang ◽  
F. G. Liu ◽  
X. G. Sun ◽  
L. Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Cancer Susceptibility ◽  
Vital Role ◽  
Migration And Invasion ◽  
Tumor Tissues ◽  
Hcc Cells

Abstract Purpose Long non-coding RNAs (lncRNAs) have been shown to play important roles in tumorigenesis, but their biological functions and the underlying molecular mechanisms remain unclear. Alternative splicing of five exons results in three transcript variants of cancer susceptibility 2 (CASC2): the lncRNAs CASC2a, CASC2b, and CASC2c. CASC2a/b have been found to have crucial regulatory functions in a number of malignancies, but few studies have examined the effects of CASC2c in cancers. The objective of the study was to investigate the role of CASC2c in the proliferation and apoptosis of hepatocellular carcinoma (HCC) cells. Methods This study first investigated the expression levels of CASC2c in tumor tissues, corresponding non-tumor tissues and cells using quantitative real-time polymerase chain reaction. The function and underlying molecular mechanism of CASC2c in human HCC were investigated in QGY-7703 cell line, as well as in gastric cancer (GC) cell and colorectal cancer (CRC) cell. Results In the present work, we observed that CASC2c was significantly down-regulated in HCC tissues and cells. Moreover, its overexpression remarkably inhibited the growth, migration, and invasion of HCC cells in vitro and promoted their apoptosis. Furthermore, we demonstrated that CASC2c overexpression decreased p-ERK1/2 levels in HCC, GC, and CRC cells. Interestingly, while overexpression of CASC2c decreased β-catenin expression in HCC and GC cells, it increased that in CRC cells. Conclusion The lncRNA–CASC2c has a vital role in tumorigenesis and cancer progression, and may serve as a biomarker or therapeutic target in cancer treatment via down-regulation of the ERK1/2 and Wnt/β-catenin signaling pathways.

scholarly journals CD26 upregulates proliferation and invasion in keloid fibroblasts through an IGF-1-induced PI3K/AKT/mTOR pathway

2020 ◽  
Vol 8 ◽  
Author(s):  
Yu Xin ◽  
Peiru Min ◽  
Heng Xu ◽  
Zheng Zhang ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Mammalian Target Of Rapamycin ◽  
Underlying Mechanism ◽  
Mtor Pathway ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Aberrant Expression ◽  
Proliferation And Invasion ◽  
Keloid Fibroblasts

Abstract Background Keloid is a fibrotic dermal disease characterized by an abnormal increase in fibroblast proliferation and invasion. These pathological behaviours may be related to the heterogeneity of keloid fibroblasts (KFs); however, because of a lack of effective biomarkers for KFs it is difficult to study the underlying mechanism. Our previous studies revealed that the expansion of CD26+ KFs was responsible for increased keloid proliferation and invasion capabilities; the intrinsic relationship and mechanism between CD26 and keloid is therefore worthy of further investigation. The aim of this study was to explore molecular mechanisms in the process of CD26 upregulated KFs proliferation and invasion abilities, and provide more evidence for CD26 as an effective biomarker of keloid and a new clinical therapeutic target. Methods Flow cytometry was performed to isolate CD26+/CD26− fibroblasts from KFs and normal fibroblasts. To generate stably silenced KFs for CD26 and insulin-like growth factor-1 receptor (IGF-1R), lentiviral particles encoding shRNA targeting CD26 and IGF-1R were used for transfection. Cell proliferations were analysed by cell counting kit-8 assay and 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay. Scratching assay and transwell assay were used to assess cell migration and invasion abilities. To further quantify the regulatory role of CD26 expression in the relevant signalling pathway, RT-qPCR, western blot, ELISA, PI3K activity assay and immunofluorescence were used. Results Aberrant expression of CD26 in KFs was proven to be associated with increased proliferation and invasion of KFs. Furthermore, the role of the IGF-1/IGF-1 receptor axis was also studied in CD26 and was found to upregulate KF proliferation and invasion. The PI3K/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway was shown to affect CD26-regulated KF proliferation and invasion by increasing phosphorylation levels of S6 kinase and 4E-binding protein. Conclusions CD26 can be the effective biomarker for KFs, and its expression is closely related to proliferation and invasion in keloids through the IGF-1-induced PI3K/AKT/mTOR pathway. This work provides a novel perspective on the pathological mechanisms affecting KFs and therapeutic strategies against keloids.

scholarly journals Ferritin Light Chain (FTL) competes with long noncoding RNA Linc00467 for miR-133b binding site to regulate chemoresistance and metastasis of colorectal cancer

2019 ◽  
Vol 41 (4) ◽  
pp. 467-477 ◽  
Author(s):  
Zengyao Li ◽  
Jing Liu ◽  
Hang Chen ◽  
Ye Zhang ◽  
Haoze Shi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Light Chain ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Cell Resistance ◽  
Biological Functions ◽  
Study Gene Expression

Abstract Although the colorectal cancer (CRC) mortality rates are decreasing in virtue of CRC screening and improved therapeutic methods, CRC is still a leading cause of cancer deaths. One of the main causes is chemoresistance occurrence in CRC. Understanding of the molecular mechanisms of chemoresistance benefits to CRC diagnosis and treatment. In this study, gene expression was determined by western blot and qRT-PCR. The biological functions of genes in CRC cells were studied by knocking down or overexpressing the gene in CRC cells and then analyzing cell sensitivity to 5-Fu by the MTT assay and the flow cytometry, and analyzing cell migration and invasion by transwell assays. The luciferase reporter assay was used to examine microRNA regulation of target gene expression, and biotin pull-down assay was performed to detect interaction between RNA molecules. This study found that ferritin light chain (FTL) and long intergenic noncoding RNA Linc00467 were both upregulated in CRC tissues and cell lines, and inversely correlated to CRC patient survival. FTL and Linc00467 promoted CRC cells abilities to resistance against 5-fluor-ouracil (5-Fu), migration and invasion. These effects were compromised by miR-133b which targeted both FTL and Linc00467. miR-133b interacted with Linc00467 and miR-133b inhibitor prevented Linc00467 knockdown-induced alternations of FTL expression and biological functions. Both FTL and Linc00467 are oncogenes in CRC. FTL expression upregulated in CRC via Linc00467/ miR-133b axis, and leads to CRC cell resistance against 5-FU treatment and promotes CRC metastasis. FTL expression upregulated in CRC via Linc00467/miR-133b axis, and leads to CRC cell resistance to 5-FU treatment and promotes CRC metastasis.

scholarly journals Long noncoding RNA TTN-AS1 promotes breast cancer cell migration and invasion via sponging miR-140-5p

2020 ◽  
Author(s):  
Yusheng Li ◽  
Fan Wang
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Noncoding Rna ◽  
Vital Role ◽  
Biological Behavior ◽  
Migration And Invasion ◽  
Behavior Changes ◽  
Cell Migration And Invasion ◽  
Rna Immunoprecipitation

Abstract Objectives Breast cancer (BC) is one of the most ordinary fatal cancers. Recent studies have identified the vital role of long noncoding RNAs (lncRNAs) in the development and progression of BC. In this research, lncRNA TTN-AS1 was studied to identify how it functioned in the metastasis of BC.Methods TTN-AS1 expression of tissues was detected by RT-qPCR in 56 BC patients. Wound healing assay and transwell assay were used to observe the biological behavior changes of BC cells through gain or loss of TTN-AS1. In addition, luciferase assays and RNA immunoprecipitation (RIP) assay were performed to discover the potential targets of TTN-AS1 in BC cells.Results TTN-AS1 expression level in BC samples was higher than that of adjacent ones. Besides, cell migrated ability and cell invaded ability of BC cells were inhibited after TTN-AS1 was silenced. Cell migrated ability and cell invaded ability of BC cells were promoted after TTN-AS1 was overexpressed. In addition, miR-140-5p was upregulated after silence of TTN-AS1 in BC cells, while miR-140-5p was downregulated after overexpression of TTN-AS1 in BC cells. Furthermore, luciferase assays and RNA immunoprecipitation assay (RIP) showed that miR-140-5p was a direct target of TTN-AS1 in BC.Conclusion Our study uncovers a new oncogene in BC and suggests that TTN-AS1 could enhance BC cell migration and invasion via sponging miR-140-5p, which provides a novel therapeutic target for BC patients.

scholarly journals LncRNA GSTM3TV2 Promotes Cell Proliferation and Invasion via miR-597/FOSL2 Axis in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yuting Hu ◽  
Wei Qiu ◽  
Zhijun Kong ◽  
Siyuan Wu ◽  
Yi Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Noncoding Rna ◽  
Vital Role ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Tumor Tissues ◽  
Reporter Assays ◽  
Proliferation And Invasion

Mounting evidence has recently shown that role of long noncoding RNA is critical in many human cancers. lncRNA GSTM3TV2 was first proven to play a vital role in pancreatic cancer. However, the mechanism of lncRNA GSTM3TV2 in hepatocellular carcinoma (HCC) is still uncovered. Here, we object to distinguish the expression of lncRNA GSTM3TV2 and reveal its mechanistic relationship with HCC. We observed that the expression of lncRNA GSTM3TV2 and FOSL2 were upregulated in HCC. Knockdown of lncRNA GSTM3TV2 significantly inhibited cell proliferation. Meanwhile, the migration and invasion of HCC cells were greatly decreased by the downregulated lncRNA GSTM3TV2. The luciferase reporter assays showed that lncRNA GSTM3TV2 could be directly bound to miR-597, and the level of miR-597 was also decreased in the tumor tissues. lncRNA GSTM3TV2 could stabilize FOSL2 expression, resulting in the oncogenic properties of lncRNA GSTM3TV2 in HCC. Our study indicated the oncogenic activities of lncRNA GSTM3TV2 and emphasized the role of the miR-597/FOSL2 signaling pathway.

scholarly journals Circ_0044516 Regulates miR-136/MAT2A Pathway to Facilitate Lung Cancer Development

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yue-Wei Chen ◽  
Qiu-Rong Du ◽  
Yu-Juan He ◽  
Wen-Shu Chen ◽  
Wen-Yang Jiang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Circular Rna ◽  
Vital Role ◽  
Migration And Invasion ◽  
Lung Cancer Patients

Circular RNA (circRNA) is a type of noncoding RNA that can interact with miRNAs to regulate gene expression. However, little is known concerning circRNA, which is crucial in the pathogenesis of lung cancer. To date, limited studies have explored the role of circ_0044516 in lung cancer progression. Recently, we observed that circ_0044516 expression levels were obviously elevated in lung cancer tissues and cells. A549 and SPCA1 cells were transfected with circ_0044516 siRNA. We observed that knockdown of circ_0044516 dramatically repressed cell proliferation, increased cell apoptosis, and repressed the cell cycle. Moreover, A549 and SPCA1 cell migration and invasion abilities were greatly repressed by circ_0044516 siRNA. Due to accumulating evidence demonstrating the vital role of cancer stem cells, their mechanism of involvement has drawn increasing attention in tumor progression and metastasis research. We also found that cancer stem cell properties were restrained by silencing circ_0044516 in A549 and SPC-A1 cells. Moreover, in vivo xenograft experiments showed that circ_0044516 downregulation reduced tumor growth. Mechanistically, in lung cancer and using bioinformatics, we demonstrated that circ_0044516 sponges miR-136 targeting MAT2A. Furthermore, rescue assays were carried out to identify that circ_0044516 modulates cell proliferation, invasion, and stemness by regulating miR-136 and MAT2A in lung cancer. In summary, our study revealed that the circ_0044516/miR-136/MAT2A axis is involved in lung cancer progression. Our findings may provide novel targets for diagnosis and therapeutic intervention in lung cancer patients.

scholarly journals Long Noncoding RNA WT1-AS Inhibit Cell Malignancy via miR-494-3p in Glioma

2020 ◽  
Vol 19 ◽  
pp. 153303382091975
Author(s):  
Guangting Qiu ◽  
Wenjie Tong ◽  
Chenghao Jiang ◽  
Qingsong Xie ◽  
Jingfang Zou ◽  
...  
Keyword(s):  
Cell Lines ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Aberrant Expression ◽  
Common Causes ◽  
Associated Conditions ◽  
Ionizing Radiations

Primary brain tumors are a rare occurrence in comparison to other malignancies, the most predominant form being glioma. Commonly, exposure to ionizing radiations and inheritance of associated conditions such a neurofibromatosis and tuberous sclerosis are the most common causes of development of glioma. However, understanding of the molecular mechanisms that drive glioma development is limited. We explore the role of aberration of microRNA namely miR-494-3p through long noncoding RNA WT1-AS in the development of gliomas. In this study, we found that, levels of WT1-AS were significantly reduced in glioma tissues and cell lines. The miR-494-3p levels were negatively correlated with WT1-AS levels. The cellular proliferation and invasiveness decreased in WT1-AS transfected cell lines. Further the half maximal inhibitory concentration (IC50) of chemotherapeutic agent temozolomide was significantly reduced in the presence of WT1-AS. The cotransfection of WT1-AS and miR-494-3p reduced activation of phospho-AKT (p-AKT). Expression of miR-494-3p is modulated by binding to long noncoding RNA WT1-AS. Deregulation of WT1-AS leads to aberrant expression of miR-494-3p leading to hyperactivation of AKT. This malformation may result in altering protective immune responses in malignancies. Targeting of WT1-AS, miR-494-3p, and AKT may be novel therapeutic options in treatment of glioma.

scholarly journals Long Noncoding RNA LIFR-AS1: A New Player in Human Cancers

2022 ◽  
Vol 2022 ◽  
pp. 1-11
Author(s):  
Zhiqun Bai ◽  
Xuemei Wang ◽  
Zhen Zhang
Keyword(s):  
Leukemia Inhibitory Factor ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Clinicopathological Characteristics ◽  
Vital Role ◽  
Tumor Proliferation ◽  
Biological Processes ◽  
Leukemia Inhibitory Factor Receptor ◽  
Human Cancers

Emerging evidence has indicated that aberrantly expressed long noncoding RNAs (lncRNAs) play a vital role in various biological processes associated with tumorigenesis. Leukemia inhibitory factor receptor antisense RNA1 (LIFR-AS1) is a recently identified lncRNA transcribed in an antisense manner from the LIFR gene located on human chromosome 5p13.1. LIFR-AS1 regulates tumor proliferation, migration, invasion, apoptosis, and drug resistance through different mechanisms. Its expression level is related to the clinicopathological characteristics of tumors and plays a key role in tumor occurrence and development. In this review, we summarize the role of LIFR-AS1 in the development and progression of different cancers and highlight the potential for LIFR-AS1 to serve as a biomarker and therapeutic target for a variety of human cancers.

scholarly journals A Unique Role Of TRPV1 Ion Channels In The Suppression Of Gastric Cancer Development

2020 ◽  
Author(s):  
Nannan Gao ◽  
Feng Yang ◽  
Siyuan Chen ◽  
Hanxing Wan ◽  
Xiaoyan Zhao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Peritoneal Dissemination ◽  
Migration And Invasion ◽  
Transient Receptor Potential Vanilloid ◽  
Aberrant Expression ◽  
Trpv1 Channels

Abstract Background: Although the aberrant expression and function of most Ca2+-permeable channels are known to promote gastrointestinal tumors, the association of transient receptor potential vanilloid receptor 1(TRPV1) channels and gastric cancer (GC) has not been explored so far. We sought to determine their role in the development of GC and to elucidate the underlying molecular mechanisms. Methods: The expression of TRPV1 in GC cells and tissues was detected by qPCR, immunohistochemistry, western blot analysis and immunofluorescence. CCK8 and flow cytometry were used to detect the proliferation and cell cycle, while transwell assay was used to detect migration and invasion. The role of TRPV1 in GC development in vivo was tested using tumor xenograft and peritoneal dissemination assays in nude mice. Results: The decreased expression of TRPV1 protein in primary human GC tissues was closely correlated with poor prognosis of GC patients. TRPV1 protein was predominately expressed on the plasma membrane of several GC cell lines. TRPV1 overexpression attenuated proliferation, migration and invasion of GC cells in vitro, but TRPV1 knockdown increased them. Moreover, TRPV1 significantly reduced gastric tumor sizes, numbers and peritoneal dissemination in vivo. Mechanistically, TRPV1 overexpression increased [Ca2+]i, activated CaMKKβ and AMPK phosphorylation, and decreased expression of cyclin D1 and MMP2, but TRPV1 knockdown caused the opposite effects.Conclusions: TRPV1 uniquely suppresses GC through a novel Ca2+/CaMKKβ/AMPK pathway and its downregulation is correlated with poor survival in human GC. TRPV1 upregulation and its downstream signaling may be a promising strategy for GC prevention and therapy.

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