Senescence-associated genes and non-coding RNAs function in pancreatic cancer progression.
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ABSTRACT:
SUBMITTER: Cheng Q
PROVIDER: S-EPMC7567515 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Pancreatic ductal adenocarcinoma (PDAC) is strikingly resistant to conventional therapeutic approaches. We previously demonstrated that the histone deacetylase-associated protein SIN3B is essential for oncogene-induced senescence in cultured cells. Here, using a mouse model of pancreatic cancer, we have demonstrated that SIN3B is required for activated KRAS-induced senescence in vivo. Surprisingly, impaired senescence as the result of genetic inactivation of Sin3B was associated with delayed PDAC progression and correlated with an impaired inflammatory response. In murine and human pancreatic cells and tissues, levels of SIN3B correlated with KRAS-induced production of IL-1α. Furthermore, evaluation of human pancreatic tissue and cancer cells revealed that Sin3B was decreased in control and PDAC samples, compared with samples from patients with pancreatic inflammation. These results indicate that senescence-associated inflammation positively correlates with PDAC progression and suggest that SIN3B has potential as a therapeutic target for inhibiting inflammation-driven tumorigenesis.
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Project description:Non-coding RNAs (ncRNAs) are reported to be expressed in human cancers, including pancreatic ductal adenocarcinoma (PDAC). These ncRNAs affect the growth, migration and invasion of tumor cells by regulating cell cycle and apoptosis, as well as playing important roles in epigenetic processes, transcription and post-transcriptional regulation. It is still unclear whether alterations in ncRNAs influence PDAC development and progression. Because of this, analysis based on existing data on ncRNAs, which are crucial for modulating pancreatic tumorigenesis, will be important for future research on PDAC. Here, we summarize ncRNAs with tumor-promoting functions: HOTAIR, HOTTIP, MALAT1, lncRNA H19, lncRNA PVT1, circ-RNA ciRS-7, circ-0030235, circ-RNA_100782, circ-LDLRAD3, circ-0007534, circRHOT1, circZMYM2, circ-IARS, circ-RNA PDE8A, miR-21, miR-155, miR-221/222, miR-196b, miR-10a. While others including GAS5, MEG3, and lncRNA ENST00000480739, has_circ_0001649, miR-34a, miR-100, miR-217, miR-143 inhibit the proliferation and invasion of PDAC. Hence, we summarize the functions of ncRNAs in the occurrence, development and metastasis of PDAC, with the goal to provide guidance in the clinical diagnosis and treatment of PDAC.
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Project description:Ever since RNA sequencing of whole genomes and transcriptomes became available, numerous RNA transcripts without having the classic function of encoding proteins have been discovered. Long non-coding RNAs (lncRNAs) with a length greater than 200 nucleotides were considered as "junk" in the beginning, but it has increasingly become clear that lncRNAs have crucial roles in regulating a variety of cellular mechanisms and are often deregulated in several diseases, such as cancer. Lung cancer is the leading cause of cancer-related deaths and has a survival rate of less than 10%. Immune cells infiltrating the tumor microenvironment (TME) have been shown to have a great effect on tumor development with macrophages being the major cell type within the TME. Macrophages can inherit an inflammatory M1 or an anti-inflammatory M2 phenotype. Tumor-associated macrophages, which are predominantly polarized to M2, favor tumor growth, angiogenesis, and metastasis. In this review, we aimed to describe the complex roles and functions of lncRNAs in macrophages and their influence on lung cancer development and progression through the TME.
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Project description:Lung cancer is the most prevalent and deadliest cancer worldwide. A significant part of lung cancer studies is dedicated to the expression alterations of non-coding RNAs. The non-coding RNAs are transcripts that cannot be translated into proteins. While the study of microRNAs and siRNAs in lung cancer received a lot of attention over the last decade, highly efficient therapeutic option or the diagnostic methods based on non-coding RNAs are still lacking. Because of this, it is of utmost importance to direct future research on lung cancer towards analyzing other RNA types for which the currently available data indicates that are essential at modulating lung tumorigenesis. Through our review of studies on this subject, we identify the following non-coding RNAs as tumor suppressors: ts-46, ts-47, ts-101, ts-53, ts-3676, ts-4521 (tRNA fragments), SNORD116-26, HBII-420, SNORD15A, SNORA42 (snoRNAs), piRNA-like-163, piR-35127, the piR-46545 (piRNAs), CHIAP2, LOC100420907, RPL13AP17 (pseudogenes), and uc.454 (T-UCR). We also found non-coding RNAs with tumor-promoting function: tRF-Leu-CAG, tRNA-Leu, tRNA-Val (tRNA fragments), circ-RAD23B, circRNA 100146, circPVT1, circFGFR3, circ_0004015, circPUM1, circFLI1, circABCB10, circHIPK3 (circRNAs), SNORA42, SNORA3, SNORD46, SNORA21, SNORD28, SNORA47, SNORD66, SNORA68, SNORA78 (snoRNAs), piR-65, piR-34871, piR-52200, piR651 (piRNAs), hY4 5' fragments (YRNAs), FAM83A-AS1, WRAP53, NKX2-1-AS1 (NATs), DUXAP8, SFTA1P (pseudogene transcripts), uc.338, uc.339 (T-UCRs), and hTERC.
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Project description:Numerous studies have sought to decipher the genetic and other mechanisms contributing to β-cell loss and dysfunction in diabetes mellitus. However, we have yet to fully understand the etiology of the disease or to develop satisfactory treatments. Since the majority of diabetes susceptibility loci are mapped to non-coding regions within the genome, understanding the functions of non-coding RNAs in β-cell biology might provide crucial insights into the pathogenesis of type 1 (T1D) and type 2 (T2D) diabetes. During the past decade, numerous studies have indicated that long non-coding RNAs play important roles in the maintenance of β-cell mass and function. Indeed, lncRNAs have been shown to be involved in controlling β-cell proliferation during development and/or β-cell compensation in response to hyperglycaemia. LncRNAs such as TUG-1 and MEG3 play a role in both β-cell apoptosis and function, while others sensitize β-cells to apoptosis in response to stress signals. In addition, several long non-coding RNAs have been shown to regulate the expression of β-cell-enriched transcription factors in cis or in trans. In this review, we provide an overview of the roles of lncRNAs in maintaining β-function and mass, and discuss their relevance in the development of diabetes.
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