scholarly journals Long Non-Coding RNAs: “Key Orchestrators” in Cancers

2018 ◽  
Author(s):  
Venkata Narasimha Kadali

Long Non-Coding RNAs (lncRNAs) attaining impeccable attention in recent times owing to their expanded roles in the cell. They essentially perform a decisive task to regulate the genes in conjunction with developmental processes. In cancers the lncRNAs involves in the cell proliferation, migration and invasion made them as “key Orchestrators”. In this precise opinion, we brief the role of lncRNAs in cancer with a note on their protein coding potential.

Author(s):  
Chunying Zhang ◽  
Lin Yang ◽  
Ge Zhao ◽  
Jiaxiang Wang ◽  
Juntao Pan ◽  
...  

Neuroblastoma (NBL) exists as the most common solid malignancy which predominantly occurs in children. Long non-coding RNAs (lncRNAs) have been widely confirmed to exert functions in modulating the pathogenesis of diverse diseases. Nevertheless, whether the putative function of long intergenic non-protein coding RNA 1518 (LINC01518) in NBL has not been elucidated yet. In this study, RT-qPCR was used for determining LINC01518 expression and LINC01518 was found to be notably overexpressed in NBL tissues and cell lines compared with normal nerve tissues and cell lines. Functional experiments and mechanism assays were respectively done for the investigation into cell phenotype and for the exploration of correlation among genes. LINC01518 silencing was discovered to repress cell malignant phenotype. We observed that GATA binding protein 3 (GATA3) was an active transcription factor of LINC01518. Besides, LINC01518 functioned as a competing endogenous RNA (ceRNA), which sequestered microRNA-206 (miR-206) to up-regulate protein kinase cAMP-activated catalytic subunit beta (PRKACB). Afterwards, rescue assays validated the oncogenic role of GATA3/LINC01518/miR-206/PRKACB axis in NBL. To be summarized, our research determined that LINC01518 might be used as a putative molecular marker for NBL diagnosis and treatment.


2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Zhaoxia Xia ◽  
Xiaoxi Yang ◽  
Shuduan Wu ◽  
Zhizhen Feng ◽  
Lei Qu ◽  
...  

Abstract Our study aimed to investigate the role of long non-coding RNAs (lncRNA) TP73-AS1 in retinoblastoma (Rb). In the present study, we found that TP73-AS1 was up-regulated, while miR-139–3p was down-regulated in Rb. TP73-AS1 and miR-139-3p were inversely correlated in Rb tissues. In cells of Rb cell lines, overexpression of miR-139-3p failed to affect TP73-AS1, while TP73-AS1 overexpression caused the down-regulated miR-139-3p. TP73-AS1 overexpression caused promoted proliferation of Rb cells but showed no significant effects on cell migration and invasion. miR-139-3p overexpression played an opposite role and attenuated the effects of TP73-AS1 overexpression. Therefore, lncRNA TP73-AS1 may down-regulate miR-139-3p to promote Rb cell proliferation.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jingyu Wang ◽  
Hao Zhang ◽  
Jie Situ ◽  
Mingzhao Li ◽  
Hua Sun

Abstract Background The large involvement of long non-coding RNAs (LncRNAs) in the biological progression of numerous cancers has been reported. The function of lncRNA KCNQ1OT1 in bladder cancer (BC) remains largely unknown. This study aimed to explore the critical role of KCNQ1OT1 in BC. Materials and methods The qRT-PCR was applied to test the expression of RNAs. Cell proliferation was detected by CCK-8 and colony formation assays. Cell apoptosis was measured by TUNEL and flow cytometry experiments. Wound healing and transwell assays were employed to evaluate cell migration and invasion ability respectively. Western blot assay was used to measure relevant protein expression. Immunofluorescence (IF) staining was used to observe EMT process in BC. Results KCNQ1OT1 was significantly overexpressed in BC tissue and cell lines. KCNQ1OT1 depletion repressed cell proliferation, migration and invasion, whereas encouraged cell apoptosis. KCNQ1OT1 was a negatively/positively correlated with miR-145-5p/PCBP2 in respect with expression. Mechanically, KCNQ1OT1 was sponge of miR-145-5p and up-regulated the expression of PCBP2. MiR-145-5p inhibition and PCBP2 up-regulation could countervail the tumor-inhibitor role of KCNQ1OT1 knockdown in BC. Conclusion KCNQ1OT1 serves as competing endogenous RNA (ceRNA) to up-regulate PCBP2 via sponging miR-145-5p in BC progression.


2021 ◽  
Vol 8 ◽  
Author(s):  
Jiawen Li ◽  
Yulin Zhang ◽  
Donghui Zhang ◽  
Yifei Li

Sepsis is a syndrome with life-threatening organ dysfunction induced by a dysregulated host response to infection. The heart is one of the most commonly involved organs during sepsis, and cardiac dysfunction, which is usually indicative of an extremely poor clinical outcome, is a leading cause of death in septic cases. Despite substantial improvements in the understanding of the mechanisms that contribute to the origin and responses to sepsis, the prognosis of sepsis-induced cardiac dysfunction (SICD) remains poor and its molecular pathophysiological changes are not well-characterized. The recently discovered group of mediators known as long non-coding RNAs (lncRNAs) have presented novel insights and opportunities to explore the mechanisms and development of SICD and may provide new targets for diagnosis and therapeutic strategies. LncRNAs are RNA transcripts of more than 200 nucleotides with limited or no protein-coding potential. Evidence has rapidly accumulated from numerous studies on how lncRNAs function in associated regulatory circuits during SICD. This review outlines the direct evidence of the effect of lncRNAs on SICD based on clinical trials and animal studies. Furthermore, potential functional lncRNAs in SICD that have been identified in sepsis studies are summarized with a proven biological function in research on other cardiovascular diseases.


2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Man Huang ◽  
Jiajia Zheng ◽  
Yongya Ren ◽  
Jingjing Zhu ◽  
Linbing Kou ◽  
...  

Abstract As the most common malignant disease in childhood, children acute lymphoblastic leukemia (ALL) is a heterogeneous disease caused by the accumulated genetic alterations. Long non-coding RNAs (lncRNAs) are reported as critical regulators in diseases. GEPIA database indicated that long intergenic non-protein coding RNA 221 (LINC00221) was conspicuously down-regulated in acute myeloid leukemia. However, its expression pattern in ALL has not been revealed. This work was carried out to study the role of LINC00221 in ALL cells. Quantitative real-time PCR (qRT-PCR) quantified LINC00221 expression in ALL cells. The function of LINC00221 in ALL was determined by ki-67 immunofluorescence staining, EdU, TUNEL, JC-1, and caspase-3/8/9 activity assays. RNA pull down and Ago2-RNA immunoprecipitation (RIP) assays investigated the interaction between miR-152-3p and LINC00221 or ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 (ATP2A2). Our study revealed the low expression of LINC00221 in ALL cells. Subsequently, LINC00221 was verified to bind with miR-152-3p. Moreover, functional assays pointed out that LINC00221 overexpression posed anti-proliferation and pro-apoptosis effects in ALL cells, and these effects could be separately reversed by miR-152-3p up-regulation. Afterward, LINC00221 was revealed to regulate ATP2A2 expression via sponging miR-152-3p. Additionally, ATP2A2 was verified to involve in regulating LINC00221-mediated ALL cell proliferation and apoptosis. In conclusion, LINC00221 suppressed ALL cell proliferation and boosted ALL cell apoptosis via sponging miR-152-3p to up-regulate ATP2A2.


2012 ◽  
Vol 40 (4) ◽  
pp. 902-906 ◽  
Author(s):  
Lorna W. Harries

The central dogma of molecular biology states that DNA is transcribed into RNA, which in turn is translated into proteins. We now know, however, that as much as 50% of the transcriptome has no protein-coding potential, but rather represents an important class of regulatory molecules responsible for the fine-tuning of gene expression. Although the role of small regulatory RNAs [microRNAs and siRNAs (small interfering RNA)] is well defined, another much less characterized category of non-coding transcripts exists, namely lncRNAs (long non-coding RNAs). Pervasively expressed by eukaryotic genomes, lncRNAs can be kilobases long and regulate their targets by influencing the epigenetic control, chromatin status, mRNA processing or translation capacity of their targets. In the present review, I outline the potential mechanisms of action of lncRNAs, the cellular processes that have been associated with them, and also explore some of the emerging evidence for their involvement in common human disease.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tiantian Tang ◽  
Guiying Wang ◽  
Sihua Liu ◽  
Zhaoxue Zhang ◽  
Chen Liu ◽  
...  

AbstractThe role of organic anion transporting polypeptide 1B3 (SLCO1B3) in breast cancer is still controversial. The clinical immunohistochemical results showed that a greater proportion of patients with negative lymph nodes, AJCC stage I, and histological grade 1 (P < 0.05) was positively correlated with stronger expression of SLCO1B3, and DFS and OS were also increased significantly in these patients (P = 0.041, P = 0.001). Further subgroup analysis showed that DFS and OS were significantly enhanced with the increased expression of SLCO1B3 in the ER positive subgroup. The cellular function assay showed that the ability of cell proliferation, migration and invasion was significantly enhanced after knockdown of SLCO1B3 expression in breast cancer cell lines. In contrast, the ability of cell proliferation, migration and invasion was significantly reduced after overexpress the SLCO1B3 in breast cancer cell lines (P < 0.05). Overexpression or knockdown of SLCO1B3 had no effect on the apoptotic ability of breast cancer cells. High level of SLCO1B3 expression can inhibit the proliferation, invasion and migration of breast cancer cells, leading to better prognosis of patients. The role of SLCO1B3 in breast cancer may be related to estrogen. SLCO1B3 will become a potential biomarker for breast cancer diagnosis and prognosis assessment.


2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Xiaoguang Gu ◽  
Jianan Zhang ◽  
Yajuan Ran ◽  
Hena Pan ◽  
JinHong Jia ◽  
...  

AbstractCircular RNAs have been reported to play significant roles in regulating pathophysiological processes while also guiding clinical diagnosis and treatment of hepatocellular carcinoma (HCC). However, only a few circRNAs have been identified thus far. Herein, we investigated the role of a specific closed-loop structure of hsa_circ_101555 that was generated by back-splicing of the host gene casein kinase 1 gamma 1 (CSNK1G1) in the development and proliferation of HCC. We investigated the expression of Hsa_circ_101555 in HCC and normal tissues using bioinformatics. The expression level of hsa_circ_101555 was further detected by fluorescence in situ hybridization and qRT-PCR in ten HCC patients. Transwell, migration, WST-1 assays, and colony formation assays were used to evaluate the role of hsa_circ_101555 in HCC development and proliferation. The regulatory mechanisms of hsa_circ_101555 in miR-145-5p and CDCA3 were determined by dual luciferase reporter assay. A mouse xenograft model was also used to determine the effect of hsa_circ_101555 on HCC growth in vivo. hsa_circ_101555 showed greater stability than the linear RNA; while in vitro and in vivo results demonstrated that hsa_circ_101555 silencing significantly suppressed cell proliferation, migration, and invasion of HCC cells. Rescue experiments further demonstrated that suppression of miR-145-5p significantly attenuated the biological effects of hsa_circ_101555 knockdown in HCC cells. We also identified a putative oncogene CDCA3 as a potential miR-145-5p target. Thus, our results demonstrated that hsa_circ_101555 might function as a competing endogenous RNA of miR-145-5p to upregulate CDCA3 expression in HCC. These findings suggest that hsa_circ_101555 may be a potential therapeutic target for patients with HCC.


2021 ◽  
Vol 22 (6) ◽  
pp. 3151 ◽  
Author(s):  
Roberto Piergentili ◽  
Simona Zaami ◽  
Anna Franca Cavaliere ◽  
Fabrizio Signore ◽  
Giovanni Scambia ◽  
...  

Endometrial cancer (EC) has been classified over the years, for prognostic and therapeutic purposes. In recent years, classification systems have been emerging not only based on EC clinical and pathological characteristics but also on its genetic and epigenetic features. Noncoding RNAs (ncRNAs) are emerging as promising markers in several cancer types, including EC, for which their prognostic value is currently under investigation and will likely integrate the present prognostic tools based on protein coding genes. This review aims to underline the importance of the genetic and epigenetic events in the EC tumorigenesis, by expounding upon the prognostic role of ncRNAs.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Claudia Bello-Alvarez ◽  
Ignacio Camacho-Arroyo

Abstract Background As in other types of cancers, sex is an essential factor in the origin and progression of glioblastomas. Research in the field of endocrinology and cancer suggests that gonadal steroid hormones play an important role in the progression and prevalence of glioblastomas. In the present review, we aim to discuss the actions and mechanism triggered by gonadal steroid hormones in glioblastomas. Main body Glioblastoma is the most common malignant primary brain tumor. According to the epidemiological data, glioblastomas are more frequent in men than in women in a 1.6/1 proportion both in children and adults. This evidence, and the knowledge about sex influence over the prevalence of countless diseases, suggest that male gonadal steroid hormones, such as testosterone, promote glioblastomas growth. In contrast, a protective role of female gonadal steroid hormones (estradiol and progesterone) against glioblastomas has been questioned. Several pieces of evidence demonstrate a variety of effects induced by female and male gonadal steroid hormones in glioblastomas. Several studies indicate that pregnancy, a physiological state with the highest progesterone and estradiol levels, accelerates the progression of low-grade astrocytomas to glioblastomas and increases the symptoms associated with these tumors. In vitro studies have demonstrated that progesterone has a dual role in glioblastoma cells: physiological concentrations promote cell proliferation, migration, and invasion while very high doses (out physiological range) reduce cell proliferation and increases cell death. Conclusion Gonadal steroid hormones can stimulate the progression of glioblastomas through the increase in proliferation, migration, and invasion. However, the effects mentioned above depend on the concentrations of these hormones and the receptor involved in hormone actions. Estradiol and progesterone can exert promoter or protective effects while the role of testosterone has been always associated to glioblastomas progression.


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