X-Inactive-Specific Transcript: Review of Its Functions in the Carcinogenesis

Ghafouri‐Fard, Soudeh; Dashti, Sepideh; Farsi, Molood; Taheri, Mohammad; Mousavinejad, Seyed Ali

doi:10.3389/fcell.2021.690522

Cited by 14 publications

(14 citation statements)

References 116 publications

(54 reference statements)

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“…However, whether it is an oncogene or a tumor suppressor gene is not clear, and both sides has supporting reports. Even in the same tumor, there are inconsistent research results, including hepatocellular carcinoma, breast cancer, ovarian cancer and renal cell carcinoma [ 15 ]. This phenomenon also exists for osteosarcoma.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism of the function of XIST mainly includes binding chromatin modifying molecules and binding miRNAs as molecular sponges to regulate the expression of target molecules [ 15 ]. We found that XIST was mainly localized in the cytoplasm of osteosarcoma cells.…”

Section: Discussionmentioning

confidence: 99%

“…Long non coding RNA X-inactive specific transcription (XIST) is one of the earliest lncRNAs ever found to play a key role in X chromosome inactivation, which affects the progression of a variety of tumors [ 15 ]. In osteosarcoma, most studies have shown that XIST plays a role in promoting cancer.…”

Section: Introductionmentioning

confidence: 99%

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LncRNA XIST from the bone marrow mesenchymal stem cell derived exosome promotes osteosarcoma growth and metastasis through miR-655/ACLY signal

et al. 2022

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Background Long non-coding RNA X-inactive specific transcript (XIST) regulates the progression of a variety of tumors, including osteosarcoma. Bone marrow mesenchymal stem cells (BMSCs) can be recruited into osteosarcoma tissue and affect the progression by secreting exosomes. However, whether BMSCs derived exosomes transmit XIST to regulate the growth and metastasis of osteosarcoma and the related mechanism are still unclear. Method In this study, BMSCs derived exosomes were used to treat human osteosarcoma cells MG63 and 143B, and the level of XIST in BMSCs was intervened by siRNA. CCK-8, EdU, transwell assays were used to analyze the changes of cell proliferation, migration and invasion. Bioinformatics analysis, RNA pulldown and dual-luciferase reporter gene assays validated the targeted relationship of XIST with miR-655 and the interaction between miR-655 and ACLY 3’-UTR. 143B/LUC cell line was used to establish an animal model of in situ osteosarcoma to verify the found effects of XIST on osteosarcoma. Oil Red O staining, Western blot and so on were used to detect the changes of lipid deposition and protein expression. Results It was found that BMSCs derived exosomes promoted the proliferation, migration and invasion of osteosarcoma cells, and the down-regulation of XIST inhibited this effect. miR-655 mediated the role of BMSCs derived exosomal XIST in promoting the progression of osteosarcoma and down-regulation of miR-655 could reverse the effects of inhibiting XIST on the proliferation, migration and invasion of osteosarcoma cells. Meanwhile, animal level results confirmed that BMSCs derived exosomal XIST could promote osteosarcoma growth and lung metastasis by combining with miR-655. In-depth mechanism study showed that BMSCs derived exosomal XIST combined with miR-655 to increase the protein level of ACLY, which led to lipid deposition and activate β-catenin signal to promote the proliferation, migration and invasion of osteosarcoma cells. Conclusion This study showed that BMSCs derived exosomal XIST could enter osteosarcoma cells, bind and down-regulates the level of miR-655, resulting in an increase in the level of ACLY, thus increasing the lipid deposition and the activity of β-catenin signal to promote the growth and metastasis of osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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LncRNA XIST from the bone marrow mesenchymal stem cell derived exosome promotes osteosarcoma growth and metastasis through miR-655/ACLY signal

et al. 2022

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“…XIST/miR-140, miR-124/iASPP LncRNA X inactivation-specific transcript (XIST) is derived from XIST gene and is important for inactivation of X chromosome in the development of female mammals (94). It is reported that XIST is dysregulated in a variety of cancers and exerts its either tumor-suppressive or oncogenic role in tumorigenesis and progression of cancers, such as hepatocellular carcinoma, lung cancer, gastric cancer, and osteosarcoma (95)(96)(97). Recent studies indicated that XIST was overexpressed in PC and involved in regulating the cell proliferation, apoptosis, migration, and invasion (98).…”

Section: Hotair/mir-613/notch3mentioning

confidence: 99%

Long Noncoding Competing Endogenous RNA Networks in Pancreatic Cancer

et al. 2021

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Pancreatic cancer (PC) is a highly malignant disease characterized by insidious onset, rapid progress, and poor therapeutic effects. The molecular mechanisms associated with PC initiation and progression are largely insufficient, hampering the exploitation of novel diagnostic biomarkers and development of efficient therapeutic strategies. Emerging evidence recently reveals that noncoding RNAs (ncRNAs), including long ncRNAs (lncRNAs) and microRNAs (miRNAs), extensively participate in PC pathogenesis. Specifically, lncRNAs can function as competing endogenous RNAs (ceRNAs), competitively sequestering miRNAs, therefore modulating the expression levels of their downstream target genes. Such complex lncRNA/miRNA/mRNA networks, namely, ceRNA networks, play crucial roles in the biological processes of PC by regulating cell growth and survival, epithelial–mesenchymal transition and metastasis, cancer stem cell maintenance, metabolism, autophagy, chemoresistance, and angiogenesis. In this review, the emerging knowledge on the lncRNA-associated ceRNA networks involved in PC initiation and progression will be summarized, and the potentials of the competitive crosstalk as diagnostic, prognostic, and therapeutic targets will be comprehensively discussed.

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“…However, in late stage breast tumors or established BC cell lines, the Xi, or Barr body, is commonly absent, presumably due to the loss of Xi and replication of the active X chromosome (Xa) [24] and/or epigenetic erosion of the Xi [25], leading to the formation of XIST clouds in the nucleus de cient in XCI [26]. Supporting this abnormal function of XIST in post-XCI tumor cells, XIST expression in a wide variety of cancer cells suppresses or promotes tumor growth and/or metastasis [27][28][29]. Such divergent roles of XIST in cancer development and progression may re ect the fact that XIST functions as a major molecular sponge to repress a plethora of oncogenic or tumor suppressive MicroRNAs (miRNAs) and lncRNAs, leading to suppression or promotion of tumor growth and metastatic progression in a highly context-dependent manner [27][28][29].…”

Section: Introductionmentioning

confidence: 99%

XIST Regulates Breast Cancer Stem Cells by Activating Proinflammatory IL-6 Signaling

Zhu

et al. 2022

Preprint

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Background Aberrant expression of XIST, a long noncoding RNA initiating X chromosome inactivation (XCI) during early embryogenesis, is a common feature of breast cancer (BC). However, the roles of post-XCI XIST in breast carcinogenesis remain elusive. Methods In this study, we examined the expression of XIST in human BC cell (BCC) lines across the spectrum of BC subtypes. We then investigated the effect of knockdown (KD) of aberrantly expressed XIST in luminal and triple-negative (TN) BCCs on tumor growth, cancer stem cell (CSC) activities, and global gene expression. We identified the most significantly altered genes and pathways in ALDH− bulk tumor cells and ALDH+ CSCs upon XIST KD and validated the roles of these genes in regulating ALDH+ epithelial (E) versus CD24−/loCD44+/hi mesenchymal (M) CSCs. Lastly, we conducted miRNA array and luciferase reporter assays to define the molecular mechanisms of XIST in CSC regulation. Results Doxycycline (DOX) induced XIST KD markedly inhibits spheroid/colony forming capacity, tumor growth and tumor-initiating potential. This phenotype is attributed to impaired E-CSC in luminal and E- and M-CSC activities in TN BCCs. Gene expression profiling demonstrates that XIST KD most significantly affects cytokine-cytokine receptor interactions, resulting in markedly suppressed expression of proinflammatory cytokines IL-6 and IL-8 in the bulk of tumor cells. Exogenous IL-6, but not IL-8, rescues the reduced sphere-forming capacity and proportion of ALDH+ CSCs in luminal and TN BCCs following XIST KD. This suggests a mechanism whereby XIST regulates IL-6 production by bulk tumor cells, which then acts in a paracrine manner on ALDH+ CSCs that display elevated IL-6 receptor (IL6R) expression. XIST functions as a molecular sponge for MicroRNA let-7a-2-3p to derepress IL-6 expression, which in turn promotes self-renewal of ALDH+ CSCs by inducing STAT3 activation and expression of key CSC factors including c-MYC, KLF4 and SOX9. Conclusions This study supports a novel role of XIST by derepressing let-7 controlled paracrine IL-6 proinflammatory signaling to promote CSC self-renewal.

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X-Inactive-Specific Transcript: Review of Its Functions in the Carcinogenesis

Cited by 14 publications

References 116 publications

LncRNA XIST from the bone marrow mesenchymal stem cell derived exosome promotes osteosarcoma growth and metastasis through miR-655/ACLY signal

LncRNA XIST from the bone marrow mesenchymal stem cell derived exosome promotes osteosarcoma growth and metastasis through miR-655/ACLY signal

Long Noncoding Competing Endogenous RNA Networks in Pancreatic Cancer

XIST Regulates Breast Cancer Stem Cells by Activating Proinflammatory IL-6 Signaling

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