scholarly journals Epigenetic Programming of Cancer-Related Inflammation byncRNA Rheostat: Impact on Tumor Directed Immune Therapies

Author(s):  
Roshan Roy ◽  
Uttam Sharma ◽  
Rakhi Yadav ◽  
Manjit Kaur Rana ◽  
Ashok Sharma ◽  
...  

Accumulating evidences demonstrate that the host genome's epigenetic modificationsare essential for living organisms to adapt extreme conditions.DNA methylation, covalent modifications of histone, andinter-association of non-coding RNAs facilitate the cellular manifestation ofepigenetic changes in the genome. Out of various factors involved in the epigenetic programming of the host, miRNA (microRNA) and LncRNA (Long non-coding RNA) are new generationnon-coding molecules that influence a variety of cellular processes like immunity, cellular differentiation, and tumor development. During tumor development, temporal changes in miRNA/LncRNA rheostat influence sterile inflammatory responses accompanied by the changes in the carcinogenic signalling in the host. At the cellular level, this is manifested by the up-regulation of Inflammasome and inflammatory pathways, which promotes cancer-related inflammation. In view of this, we discuss the potential of lncRNA and miRNA directed interventions in regulating inflammation and tumor development in the host.

2020 ◽  
Vol 26 ◽  
Author(s):  
Bei Wang ◽  
Wen Xu ◽  
Yuxuan Cai ◽  
Chong Guo ◽  
Gang Zhou ◽  
...  

Background: CASC15, one of long non-coding RNA, is involved in the regulation of many tumor biological processes, and is expected to become a new biological therapeutic target. This paper aims to elucidate the pathophysiological function of CASC15 in various tumors. Methods: The relationship between CASC15 and tumors was analyzed by searching references, and summarizes the specific pathophysiological mechanism of CASC15. Results: LncRNA CASC15 is closely related to tumor development, and has been shown to be abnormally high expressed in all kinds of tumors, including breast cancer, cervical cancer, lung cancer, hepatocellular carcinoma, gastric cancer, bladder cancer, colon cancer, colorectal cancer, cardiac hypertrophy, intrahepatic cholangiocarcinoma, leukemia, melanoma, tongue squamous cell carcinoma, nasopharyngeal carcinoma. However, CASC15 has been found to be downexpressed abnormally in ovarian cancer, glioma and neuroblastoma. Besides, it is identified that CASC15 can affect the proliferation, invasion and apoptosis of tumors. Conclusion: LncRNA CASC15 has the potential to become a new therapeutic target or marker for a variety of tumors.


2021 ◽  
Vol 11 (6) ◽  
pp. 513
Author(s):  
Zheng Zhang ◽  
Meng Gu ◽  
Zhongze Gu ◽  
Yan-Ru Lou

Genetic polymorphisms are defined as the presence of two or more different alleles in the same locus, with a frequency higher than 1% in the population. Since the discovery of long non-coding RNAs (lncRNAs), which refer to a non-coding RNA with a length of more than 200 nucleotides, their biological roles have been increasingly revealed in recent years. They regulate many cellular processes, from pluripotency to cancer. Interestingly, abnormal expression or dysfunction of lncRNAs is closely related to the occurrence of human diseases, including cancer and degenerative neurological diseases. Particularly, their polymorphisms have been found to be associated with altered drug response and/or drug toxicity in cancer treatment. However, molecular mechanisms are not yet fully elucidated, which are expected to be discovered by detailed studies of RNA–protein, RNA–DNA, and RNA–lipid interactions. In conclusion, lncRNAs polymorphisms may become biomarkers for predicting the response to chemotherapy in cancer patients. Here we review and discuss how gene polymorphisms of lncRNAs affect cancer chemotherapeutic response. This knowledge may pave the way to personalized oncology treatments.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5997 ◽  
Author(s):  
Zunqiang Yan ◽  
Xiaoyu Huang ◽  
Wenyang Sun ◽  
Qiaoli Yang ◽  
Hairen Shi ◽  
...  

Background Clostridium perfringens (C. perfringens) type C is the most common bacteria causing piglet diarrheal disease and it greatly affects the economy of the global pig industry. The spleen is an important immune organ in mammals; it plays an irreplaceable role in resisting and eradicating pathogenic microorganisms. Based on different immune capacity in piglets, individuals display the resistance and susceptibility to diarrhea caused by C. perfringens type C. Recently, long non-coding RNA (lncRNA) and mRNA have been found to be involved in host immune and inflammatory responses to pathogenic infections. However, little is known about spleen transcriptome information in piglet diarrhea caused by C. perfringens type C. Methods Hence, we infected 7-day-old piglets with C. perfringens type C to lead to diarrhea. Then, we investigated lncRNA and mRNA expression profiles in spleens of piglets, including control (SC), susceptible (SS), and resistant (SR) groups. Results As a result, 2,056 novel lncRNAs and 2,417 differentially expressed genes were found. These lncRNAs shared the same characteristics of fewer exons and shorter length. Bioinformatics analysis identified that two lncRNAs (ALDBSSCT0000006918 and ALDBSSCT0000007366) may be involved in five immune/inflammation-related pathways (such as Toll-like receptor signaling pathway, MAPK signaling pathway, and Jak-STAT signaling pathway), which were associated with resistance and susceptibility to C. perfringens type C infection. This study contributes to the understanding of potential mechanisms involved in the immune response of piglets infected with C. perfringens type C.


2020 ◽  
Vol 35 (1) ◽  
pp. 10-18 ◽  
Author(s):  
Mingzhu Lin ◽  
Yinyan Li ◽  
Jianfeng Xian ◽  
Jinbin Chen ◽  
Yingyi Feng ◽  
...  

Objective: Abundant evidence has illustrated that long non-coding RNA (lncRNA) plays a vital role in the regulation of tumor development and progression. Ectopic expression of a novel lncRNA, termed lnc-AGER-1, has been discovered in cancers, and this lncRNA was reported to exert an anti-tumor effect. However, its biological mechanism remains unelucidated in colorectal cancer. Methods: A total of 159 paired colorectal cancer specimens and adjacent tissues was applied to detect the expression of lnc-AGER-1 by the quantitative Real-time PCR (qRT-PCR), and a series of functional assays was executed to uncover the role of this lncRNA on colorectal cancer. Results: We found that the expression of lnc-AGER-1 in the tumor tissues was significantly down-regulated, while compared with adjacent normal tissues (0.0115 ± 0.0718 vs. 0.0347 ± 0.157; P < 0.0001). Also, lnc-AGER-1 was observably associated with clinical T status (r = −0.184, P = 0.024). Patients with advanced T status exerted a significantly lower level of lnc-AGER-1 than those with early T status (20.0% vs. 40.7%, P = 0.021). Over-expression of lnc-AGER-1 inhibited cell proliferation and migration efficiency, and induced cell cycle arrest at the G0/G1 phase, and promoted cell apoptosis. Further research proved that lnc-AGER-1 altered the expression of its neighbor gene, AGER, through acting as a competing endogenous RNA for miR-182 in colorectal cancer. Conclusion: lnc-AGER-1 has a suppressive role in colorectal cancer development via modulating AGER, which may serve as a target for colorectal cancer diagnosis and treatment.


2021 ◽  
Vol 8 ◽  
Author(s):  
Qingshui Wang ◽  
Youyu Lin ◽  
Wenting Zhong ◽  
Yu Jiang ◽  
Yao Lin

The death associated protein kinases (DAPKs) are a family of calcium dependent serine/threonine kinases initially identified in the regulation of apoptosis. Previous studies showed that DAPK family members, including DAPK1, DAPK2 and DAPK3 play a crucial regulatory role in malignant tumor development, in terms of cell apoptosis, proliferation, invasion and metastasis. Accumulating evidence has demonstrated that non-coding RNAs, including microRNA (miRNA), long non-coding RNA (lncRNA) and circRNA, are involved in the regulation of gene expression and tumorigenesis. Recent studies indicated that non-coding RNAs participate in the regulation of DAPKs. In this review, we summarized the current knowledge of non-coding RNAs, as well as the potential miRNAs, lncRNAs and circRNAs, that are involved in the regulation of DAPKs.


Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2008 ◽  
Author(s):  
Priyanka Gokulnath ◽  
Tiziana de Cristofaro ◽  
Ichcha Manipur ◽  
Tina Di Palma ◽  
Amata Amy Soriano ◽  
...  

High-Grade Serous Ovarian Carcinoma (HGSC) is the most incidental and lethal subtype of epithelial ovarian cancer (EOC) with a high mortality rate of nearly 65%. Recent findings aimed at understanding the pathogenesis of HGSC have attributed its principal source as the Fallopian Tube (FT). To further comprehend the exact mechanism of carcinogenesis, which is still less known, we performed a transcriptome analysis comparing FT and HGSC. Our study aims at exploring new players involved in the development of HGSC from FT, along with their signaling network, and we chose to focus on non-coding RNAs. Non-coding RNAs (ncRNAs) are increasingly observed to be the major regulators of several cellular processes and could have key functions as biological markers, as well as even a therapeutic approach. The most physiologically relevant and significantly dysregulated non-coding RNAs were identified bioinformatically. After analyzing the trend in HGSC and other cancers, MAGI2-AS3 was observed to be an important player in EOC. We assessed its tumor-suppressive role in EOC by means of various assays. Further, we mapped its signaling pathway using its role as a miRNA sponge to predict the miRNAs binding to MAGI2AS3 and showed it experimentally. We conclude that MAGI2-AS3 acts as a tumor suppressor in EOC, specifically in HGSC by sponging miR-15-5p, miR-374a-5p and miR-374b-5p, and altering downstream signaling of certain mRNAs through a ceRNA network.


2019 ◽  
Vol 44 (1) ◽  
pp. 317-326 ◽  
Author(s):  
Wei‐Jun Liang ◽  
Xiao‐Yuan Zeng ◽  
Sha‐Li Jiang ◽  
Hong‐Yi Tan ◽  
Mu‐Yun Yan ◽  
...  

Author(s):  
Chengyu Hu ◽  
Kai Liu ◽  
Bei Wang ◽  
Wen Xu ◽  
Yexiang Ling ◽  
...  

Background: There is increasing evidence that lncRNA, a type of transcript which is over 200 nucleotides in length may serve as oncogenes or suppressor genes are implicated in the pathophysiology of human diseases. In particular, tumorigenesis and progress are closely correlated with its abnormal expression. In addition, it may become a promising target for many oncology biotherapies. Abnormal DLX6-AS1 expression affects different cellular processes such as proliferation, aggression and metastasis. This review aims to probe into the pathophysiological functions and molecular mechanisms of DLX6-AS1 in various cancers. Methods: By retrieving the literature, this review summarizes the biological function and mechanism of LncRNA DLX6- AS1 in tumor occurrence. Results: The lncRNA DLX6-AS1 is a new tumor-related RNA that has recently been found to be aberrantly expressed in a divers cancers, containing pancreatic cancer, osteosarcoma, non-small cell lung cancer, gastric carcinoma, glioma, hepatocellular cancer, colorectal carcinoma, renal carcinoma, esophageal squamous cell cancer, ovarian cancer, Ewing sarcoma, cervical cancer, breast cancer, thyroid cancer, neuroblastoma, pulmonary adenocarcinoma, nasopharyngeal carcinoma, squamous laryngeal cancer and bladder cancer, etc. Meanwhile, it is identified DLX6-AS1 regulates the aggression, translocation and proliferation of diverse cancers. Conclusion: LncRNA DLX6-AS1 may be viable markers in tumors or a potential therapeutic target for multiple tumors.


RNA Biology ◽  
2015 ◽  
Vol 13 (1) ◽  
pp. 98-108 ◽  
Author(s):  
Xiao Zhou ◽  
Xiaorui Han ◽  
Ann Wittfeldt ◽  
Jingzhi Sun ◽  
Chujun Liu ◽  
...  

2018 ◽  
Vol 4 (3) ◽  
pp. 17 ◽  
Author(s):  
John S. Mattick

Transcriptomic studies have demonstrated that the vast majority of the genomes of mammals and other complex organisms is expressed in highly dynamic and cell-specific patterns to produce large numbers of intergenic, antisense and intronic long non-protein-coding RNAs (lncRNAs). Despite well characterized examples, their scaling with developmental complexity, and many demonstrations of their association with cellular processes, development and diseases, lncRNAs are still to be widely accepted as major players in gene regulation. This may reflect an underappreciation of the extent and precision of the epigenetic control of differentiation and development, where lncRNAs appear to have a central role, likely as organizational and guide molecules: most lncRNAs are nuclear-localized and chromatin-associated, with some involved in the formation of specialized subcellular domains. I suggest that a reassessment of the conceptual framework of genetic information and gene expression in the 4-dimensional ontogeny of spatially organized multicellular organisms is required. Together with this and further studies on their biology, the key challenges now are to determine the structure–function relationships of lncRNAs, which may be aided by emerging evidence of their modular structure, the role of RNA editing and modification in enabling epigenetic plasticity, and the role of RNA signaling in transgenerational inheritance of experience.


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