X-inactive-specific transcript: A long noncoding RNA with complex roles in human cancers

Yang, Zhi; Jiang, Xiaodi; Jiang, Xiaofeng; Zhao, Haiying

doi:10.1016/j.gene.2018.08.071

Cited by 62 publications

(55 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…XIST is a long noncoding RNA known for its role in X chromosome inactivation in mammals and is associated with solid tumors. 11 To our knowledge, its role in myeloma has not been described. SLITRK4 encodes a transmembrane protein of the SLITRK family highly expressed in the brain and adrenal glands and suppresses neurite growth.…”

Section: Gep Analysismentioning

confidence: 95%

A pilot study of pembrolizumab in smoldering myeloma: report of the clinical, immune, and genomic analysis

Manasanch¹,

Han

Mathur³

et al. 2019

Blood Advances

View full text Add to dashboard Cite

Multiple myeloma is, in most patients, an incurable cancer. Its precursors can be identified with routine tests setting the stage for early intervention to prevent active myeloma. We investigated the efficacy and safety of pembrolizumab, an antiprogrammed cell death 1 antibody, in smoldering myeloma patients with intermediate/high risk of progression to symptomatic myeloma. Thirteen patients were treated with a median number of 8 cycles. One patient achieved a stringent complete response with bone marrow next-generation sequencing negativity at 10−4 that is ongoing at 27 months (8%); 11 had stable disease (85%), and 1 progressed (8%). Three patients discontinued therapy due to immune-related adverse events: 2 with transaminitis and 1 due to tubulointerstitial nephritis. Immune profiling of bone marrow samples at baseline showed markers associated with a preexisting immune response in the responder compared with nonresponders and features of increased T-cell exhaustion in nonresponders. Consistent with this, transcriptome sequencing of bone marrow samples at baseline revealed an increased interferon-γ signature in the responder compared with the nonresponders. In summary, our results suggest that smoldering myeloma may be immunogenic in a subset of patients, and therapies that enhance antitumor T-cell responses may be effective in preventing its progression. This trial was registered at www.clinicaltrials.gov as #NCT02603887.

show abstract

Section: Gep Analysismentioning

confidence: 95%

A pilot study of pembrolizumab in smoldering myeloma: report of the clinical, immune, and genomic analysis

Manasanch¹,

Han

Mathur³

et al. 2019

Blood Advances

View full text Add to dashboard Cite

show abstract

“…XIST and other lncRNAs of the X inactivation center (XIC) may have more direct roles in tumor risk as well. XIST appears to be both tumor-promoting and tumorsuppressive, depending on cancer type and context [118]. Surprisingly, two meta-analyses of XIST in cancer identified no association between XIST and sex/gender, but did find that high levels were associated with poor overall survival [119,120].…”

Section: Sex Differences In Epigeneticsmentioning

confidence: 99%

Sex differences in cancer mechanisms

et al. 2020

View full text Add to dashboard Cite

We now know that cancer is many different diseases, with great variation even within a single histological subtype. With the current emphasis on developing personalized approaches to cancer treatment, it is astonishing that we have not yet systematically incorporated the biology of sex differences into our paradigms for laboratory and clinical cancer research. While some sex differences in cancer arise through the actions of circulating sex hormones, other sex differences are independent of estrogen, testosterone, or progesterone levels. Instead, these differences are the result of sexual differentiation, a process that involves genetic and epigenetic mechanisms, in addition to acute sex hormone actions. Sexual differentiation begins with fertilization and continues beyond menopause. It affects virtually every body system, resulting in marked sex differences in such areas as growth, lifespan, metabolism, and immunity, all of which can impact on cancer progression, treatment response, and survival. These organismal level differences have correlates at the cellular level, and thus, males and females can fundamentally differ in their protections and vulnerabilities to cancer, from cellular transformation through all stages of progression, spread, and response to treatment. Our goal in this review is to cover some of the robust sex differences that exist in core cancer pathways and to make the case for inclusion of sex as a biological variable in all laboratory and clinical cancer research. We finish with a discussion of lab-and clinic-based experimental design that should be used when testing whether sex matters and the appropriate statistical models to apply in data analysis for rigorous evaluations of potential sex effects. It is our goal to facilitate the evaluation of sex differences in cancer in order to improve outcomes for all patients.

show abstract

“…For example, lncRNA HOX transcript antisense RNA (HOTAIR) facilitates HSCs activation and fibrogenesis in the mouse livers . LncRNA X‐inactive‐specific transcript (XIST) is dysregulated and acts as an oncogene or a tumor suppressor in diverse malignancies . In particular, XIST is highly expressed in hepatocellular carcinoma tissues and promotes hepatocellular carcinoma progression .…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA XIST enhances ethanol‐induced hepatic stellate cells autophagy and activation via miR‐29b/HMGB1 axis

et al. 2019

View full text Add to dashboard Cite

Activation of hepatic stellate cells (HSCs) is a prominent driver of liver fibrogenesis, including alcoholic liver fibrosis (ALF). Furthermore, autophagy contributes to HSCs activation. This study aims to investigate the role and the mechanisms of long noncoding RNA XIST in regulating HSCs autophagy and activation. Human HSC cells (LX-2) were treated with 100 mmol/L ethanol to mimic HSCs activation. The HSCs activation was evaluated by determining cell viability and protein levels of fibrosis markers α-smooth muscle actin (α-SMA) and collagen type 1 α1 (CoL1A1). The autophagy was evaluated by measuring autophagy markers Beclin-1 and LC3-II. The interaction among XIST, miR-29b, and high-mobility group box-1 (HMGB1) were analyzed using luciferase reporter assay, qRT-PCR, and western blot. Lentiviruses targeting sh-XIST (LV-sh-XIST) were injected into ALF model mice via tail vein to elucidate the in vivo role of XIST in ALF injury. XIST was upregulated in ethanolactivated LX-2 cells. Furthermore, XIST served as a competitive endogenous RNA of miR-29b to facilitate HMGB1 expression, and thus enhanced ethanol-induced HSCs autophagy and activation. Further in vivo assay showed that downregulation of XIST by LV-sh-XIST alleviated ALF injury in ALF model mice. Collectively, XIST enhances ethanol-induced HSCs autophagy and activation via miR-29b/HMGB1 axis.autophagy, hepatic stellate cells activation, HMGB1, miR-29b, XIST Abbreviations: ALF, alcoholic liver fibrosis; CoL1A1, collagen type 1 α1; ceRNA, competitive endogenous RNA; HMGB, high mobility group protein B1; HMGB1, high-mobility group box-1; HSCs, hepatic stellate cells; HOTAIR, lncRNA HOX transcript antisense RNA; lncRNAs, long noncoding RNAs; LC3-II, microtubule-associated protein 1A/1B-light chain 3; LV-sh-XIST, lentiviruses targeting sh-XIST; LX-2, human HSC cells; MTT, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide; PF, pulmonary fibrosis; RNA XIST, long noncoding; si-HMGB1, small interfering RNA targeting HMGB1; siRNA, small interfering RNA; si-XIST, small interfering RNA targeting XIST; XIST, LncRNA X-inactive-specific transcript; α-SMA, α-smooth muscle actin.

show abstract

X-inactive-specific transcript: A long noncoding RNA with complex roles in human cancers

Cited by 62 publications

References 85 publications

A pilot study of pembrolizumab in smoldering myeloma: report of the clinical, immune, and genomic analysis

A pilot study of pembrolizumab in smoldering myeloma: report of the clinical, immune, and genomic analysis

Sex differences in cancer mechanisms

Long noncoding RNA XIST enhances ethanol‐induced hepatic stellate cells autophagy and activation via miR‐29b/HMGB1 axis

Contact Info

Product

Resources

About