LncRNA PRAL is closely related to clinical prognosis of multiple myeloma and the bortezomib sensitivity

Xiao, Gong‑Wei; Li, Yanqing; Wang, Yanyu; Zhao, Bingbing; Zou, Zhilan; Hou, Shuang; Jia, Xiaohong; Liu, Xi; Yao, Ye; Wan, Jun; Xiong, Hong

doi:10.1016/j.yexcr.2018.06.026

Cited by 18 publications

(15 citation statements)

References 37 publications

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“…Recently, lncRNAs have been associated with tumor initiation, progression and metastasis (12,13), and play important roles in the survival, growth, differentiation, apoptosis and regulating signal pathways in a number of tumors (14)(15)(16)(17)(18). Notably, lncRNAs have been found to be novel prognostic markers and therapeutic targets for numerous types lncRNA PART1, manipulated by transcriptional factor FOXP2, suppresses proliferation and invasion in ESCC by regulating the miR-18a-5p/SOX6 signaling axis of cancer (19,20). Prostate androgen regulated transcript 1 (PART1) is predominately expressed in the prostate and is transcriptionally regulated by androgens in prostate cancer cells (21).…”

Section: Introductionmentioning

confidence: 99%

lncRNA PART1, manipulated by transcriptional factor FOXP2, suppresses proliferation and invasion in ESCC by regulating the miR‑18a‑5p/SOX6 signaling axis

et al. 2021

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An increasing number of studies have demonstrated that long non-coding (lnc)RNAs are associated with tumor invasion, metastasis and the prognosis of patients with a variety of different tumors. However, the roles of lncRNA prostate androgen regulated transcript 1 (PART1) in esophageal squamous cell carcinoma (ESCC) remain unknown. In the present study, reverse transcription-quantitative PCR was performed to investigate the levels of PART1, SRY-box transcription factor 6 (SOX6) and miR-18a-5p in ESCC tissues and cells. The functions of PART1 in ESCC were demonstrated using Cell Counting Kit-8 and Matrigel assays. Promoter activity and dual-luciferase reporter assays, RNA immunoprecipitation and western blot analyses were also used to determine the potential mechanisms of PART1 in ESCC cell lines. It was found that PART1 and SOX6 were both downregulated in ESCC tissues and cells, and their low expression levels were associated with TNM stage, lymph node metastasis and poor prognosis in patients with ESCC. Forkhead box protein P2 (FOXP2) exhibited low expression level in ESCC tissues, and its expression was positively correlated with PART1 expression level in ESCC tissues. FOXP2 was found to bind to the promoter region of PART1 to regulate its expression in ESCC cells. Functionally, PART1 overexpression suppressed cell proliferation and invasion, whereas PART1 downregulation promoted cell proliferation and invasion in the ESCC cell lines. Mechanistically, PART1 functions as a competing endogenous (ce)RNA by sponging miR-18a-5p, resulting in the upregulation of the downstream target gene, SOX6, coupled with the inactivation of the β-catenin/c-myc signaling axis, to suppress ESCC cell proliferation and invasion. In conclusion, data from the present study unveil a potential ceRNA regulatory pathway, in which PART1 affects SOX6 expression level by sponging miR-18a-5p, to ultimately suppress ESCC development and progression.

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Section: Introductionmentioning

confidence: 99%

lncRNA PART1, manipulated by transcriptional factor FOXP2, suppresses proliferation and invasion in ESCC by regulating the miR‑18a‑5p/SOX6 signaling axis

et al. 2021

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“…For example, upregulation of lncRNA H19 promotes bortezomib resistance of multiple myeloma cells by sponging miR-29b-3p and increasing MCL-1 expression [32]. LncRNA PRAL is downregulated in primary multiple myeloma cells and cell lines, and correlated with advanced ISS stage [33]. Moreover, overexpression of PARL suppresses proliferation, induce s apoptosis and enhanced bortezomib sensitivity of multiple myeloma cells.…”

Section: Discussionmentioning

confidence: 99%

LncRNA ANRIL promotes multiple myeloma progression and bortezomib resistance by EZH2-mediated epigenetically silencing of PTEN

Yang¹,

Du²,

Liu³

et al. 2021

neo

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Multiple myeloma (MM) is a plasma cell malignancy of bone marrow. In the present study, we aimed to study the function and potential mechanism of the antisense non-coding RNA in the INK4 Locus (ANRIL) in MM. The expression levels of ANRIL in MM patients and healthy donors were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The effects and mechanisms of ANRIL in MM were evaluated by cell viability assay, BrdU incorporation assay, tumor xenograft model, flow cytometry, western blot, RNA immunoprecipitation (RIP), transcriptome RNA sequencing, and chromatin immunoprecipitation (ChIP). We found that ANRIL was upregulated in MM patients and cell lines, and associated with advanced international staging system (ISS) stage and poor overall survival. Enforced ANRIL expression promoted prolife ration and tumor xenograft growth of MM cells, while knockdown of ANRIL exhibited opposite effects. Moreover, ANRIL overexpression increased the half-maximal inhibitory concentration (IC50) of bortezomib and reduced bortezomib-induced apoptosis in MM cells. ANRIL was found to accumulate in the nucleus of MM cells, and interact with EZH2 by RIP assay. Transcriptome RNA sequencing identified PTEN as a target of ANRIL in MM cells. In ChIP assay, knockdown of ANRIL reduced EZH2 occupancy and H3K27me3 binding to the promoter region of PTEN. Furthermore, EZH2 knockout or PTEN restoration abrogated the effects caused by ANRIL overexpression in MM cells. Our results indicated that ANRIL exerted oncogenic functions and conferred chemoresistance of MM cells by EZH2-mediated epigenetically silencing of PTEN.

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“…Studies showed that MM patients with low expression of PRAL had a relatively shorter OS and disease‐free survival. Besides, functional studies reported that PRAL promoted MM cell apoptosis and sensitized MM cells to BTZ both in vitro and in vivo through targeting miR‐210, thereby releasing inhibition of bone morphogenetic protein 2 (G. Xiao et al, 2018). To note that, PRAL is located in chromosome 17p, which may partially explain the association between del(17p) and inferior prognosis in MM.…”

Section: Lncrna‐mediated Drug Resistance In MMmentioning

confidence: 99%

Roles of noncoding RNAs in drug resistance in multiple myeloma

Zou

Wan

et al. 2020

Journal Cellular Physiology

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Despite the administration of new effective drugs in recent years, relapse and drug resistance are still the main obstacles in multiple myeloma (MM) treatment, making MM an incurable disease. To overcome drug resistance in MM, it is critical to understand the underlying mechanisms of malfunctioning gene expression and develop novel targeted therapies. During the past few decades, with the discovery and characterization of noncoding RNAs (ncRNAs), the landscape of dysregulated ncRNAs of cancers as well as their biological and pathobiological functions in tumorigenesis and drug resistance have been recognized. Studies about ncRNAs improved the understanding of variations of drug response among individuals at a level distinguished from genetic polymorphism, and provided with new orientations for targeted therapies. In this review, we will summarize the emerging impact and underlying molecular mechanisms of the most relevant classes of ncRNAs in drug resistance of MM, and discuss the potential as well as strategies of treating ncRNAs as therapeutic targets.

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LncRNA PRAL is closely related to clinical prognosis of multiple myeloma and the bortezomib sensitivity

Cited by 18 publications

References 37 publications

lncRNA PART1, manipulated by transcriptional factor FOXP2, suppresses proliferation and invasion in ESCC by regulating the miR‑18a‑5p/SOX6 signaling axis

lncRNA PART1, manipulated by transcriptional factor FOXP2, suppresses proliferation and invasion in ESCC by regulating the miR‑18a‑5p/SOX6 signaling axis

LncRNA ANRIL promotes multiple myeloma progression and bortezomib resistance by EZH2-mediated epigenetically silencing of PTEN

Roles of noncoding RNAs in drug resistance in multiple myeloma

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