Long non-coding RNA LINC01268 promotes cell growth and inhibits cell apoptosis by modulating miR-217/SOS1 axis in acute myeloid leukemia

Chen, Beili; Li, Yuchuan; Nie, Yuwei; Tang, Ailin; Zhou, Qin

doi:10.1590/1414-431x20209299

Cited by 12 publications

(8 citation statements)

References 28 publications

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“…LINC01268 is an independent prognostic immune-related marker that can reduce the proliferation and metastasis of cancer cells in neuroblastoma [35]. Increased plasma levels of LINC01268 are associated with poor prognostic factors in myelo brosis [36], and LINC01268 positively regulates SOS1 expression by sponging miR-217 to promote acute myeloid leukemia cell viability and cell cycle progression but inhibit apoptosis [37]. We also identi ed that LINC01268, as an oncogene, can promote epithelial-mesenchymal transition (EMT) in PaCa through the miR-217-KIF2A-PI3K/AKT axis [24].…”

Section: Discussionmentioning

confidence: 99%

Plasma-derived exosomal long noncoding RNAs of pancreatic cancer patients as novel blood-based biomarkers of disease

He,

Chen,

et al. 2023

Preprint

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Background Pancreatic cancer (PaCa) is one of the most intractable and fatal malignancies and has been associated with the dysregulation of long noncoding RNAs (lncRNAs). However, their clinical value in pancreatic cancer is poorly explained but is essential to improve the prognosis of PaCa. Methods In this study, we analyzed the plasma-derived exosomal lncRNA profiles in patients with PaCa by whole transcriptome sequencing analysis, and the expression levels of four plasma-derived exosomal lncRNAs (LINC01268, LINC02802, AC124854.2, and AL132657.1) in PaCa plasma were validated by quantitative real-time polymerase chain reaction (qRT‒PCR). The relationship between the expression of the four lncRNAs and the clinicopathologic features of patients with PaCa was also evaluated. Results We demonstrated that exosomal LINC01268, LINC02802, AC124854.2, and AL132657.1 were highly expressed in PaCa plasma compared with normal controls and positively correlated with serum expression of CA19-9. The receiver operating characteristic curves (AUCs) of the four lncRNAs were 0.8044, 0.6587, 0.7023, and 0.6172, respectively, and the AUC value of the combination of the four exosomal lncRNAs was increased to 0.8130, with a sensitivity of 0.72 and specificity of 0.84, which suggested that plasma-derived exosomal LINC01268, LINC02802, AC124854.2, and AL132657.1 may be novel diagnostic markers for PaCa. Conclusions Our research revealed the plasma-derived exosomal long noncoding RNAs of PaCa patients were novel blood-based biomarkers of disease

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Section: Discussionmentioning

confidence: 99%

Plasma-derived exosomal long noncoding RNAs of pancreatic cancer patients as novel blood-based biomarkers of disease

He,

Chen,

et al. 2023

Preprint

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“…LINC01268 has been recently described as being upregulated in AML samples [ 52 , 53 ]. In a first work LINC01268 has been described as acting as competing endogenous RNA (ceRNA) via sponging the onco-suppressor miR-217 which in turns inhibits at the post-transcriptional level SOS1 mRNA.…”

Section: Discussionmentioning

confidence: 99%

“…In a first work LINC01268 has been described as acting as competing endogenous RNA (ceRNA) via sponging the onco-suppressor miR-217 which in turns inhibits at the post-transcriptional level SOS1 mRNA. By modulating miR-217/SOS1 regulatory axis, LINC01268 promotes cell growth and inhibits apoptosis [ 52 ]. The downregulation of miR-217 in AML cells was described also by Xiao et al, being proposed acting as a tumor suppressor by directly targeting KRAS [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, we tried to design a network of gene expression regulation by LINC01268, which demonstrates that its overexpression is one of the mechanisms underlying leukemogenesis in AML and the induction of expression of inflammatory cytokines (Figure 7). LINC01268 has been recently described as being upregulated in AML samples [52,53]. In a first work LINC01268 has been described as acting as competing endogenous RNA (ceRNA) via sponging the onco-suppressor miR-217 which in turns inhibits at the posttranscriptional level SOS1 mRNA.…”

Section: Discussionmentioning

confidence: 99%

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Increased Plasma Levels of lncRNAs LINC01268, GAS5 and MALAT1 Correlate with Negative Prognostic Factors in Myelofibrosis

Fantini

Rontauroli

Sartini

et al. 2021

Cancers

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Long non-coding RNAs (lncRNAs) have been recently described as key mediators in the development of hematological malignancies. In the last years, circulating lncRNAs have been proposed as a new class of non-invasive biomarkers for cancer diagnosis and prognosis and to predict treatment response. The present study is aimed to investigate the potential of circulating lncRNAs as non-invasive prognostic biomarkers in myelofibrosis (MF), the most severe among Philadelphia-negative myeloproliferative neoplasms. We detected increased levels of seven circulating lncRNAs in plasma samples of MF patients (n = 143), compared to healthy controls (n = 65). Among these, high levels of LINC01268, MALAT1 or GAS5 correlate with detrimental clinical variables, such as high count of leukocytes and CD34+ cells, severe grade of bone marrow fibrosis and presence of splenomegaly. Strikingly, high plasma levels of LINC01268 (p = 0.0018), GAS5 (p = 0.0008) or MALAT1 (p = 0.0348) are also associated with a poor overall-survival while high levels of LINC01268 correlate with a shorter leukemia-free-survival. Finally, multivariate analysis demonstrated that the plasma level of LINC01268 is an independent prognostic variable, suggesting that, if confirmed in future in an independent patients’ cohort, it could be used for further studies to design an updated classification model for MF patients.

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“…Chen et al. 32 found that the proportion of SOS1 inhibition cells staying in G1 phase increased compared with the NC group in SOS1 inhibition, because activation of the PI3K-AKT signaling pathway promotes malignant cell proliferation induced by BCR-ABL. Our findings provide a rationale for therapeutic targeting of SOS1 levels to inhibit the proliferation of CML cells.…”

Section: Discussionmentioning

confidence: 99%

Targeting SOS1 overcomes imatinib resistance with BCR-ABL independence through uptake transporter SLC22A4 in CML

Liu¹,

Li²,

Su³

et al. 2021

Molecular Therapy - Oncolytics

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Resistance to the BCR-ABL inhibitor imatinib mesylate poses a major problem for the treatment of chronic myeloid leukemia. Imatinib resistance often results from a secondary mutation in BCR-ABL that interferes with drug binding. However, sometimes there is no mutation in BCR-ABL, and the basis of such BCR-ABL-independent imatinib mesylate resistance remains to be elucidated. SOS1, a guanine nucleotide exchange factor for Ras protein, affects drug sensitivity and resistance to imatinib. The depletion of SOS1 markedly inhibits cell growth either in vitro or in vivo and significantly increases the sensitivity of chronic myeloid leukemia cells to imatinib. Furthermore, LC-MS/MS and RNA-seq assays reveal that SOS1 negatively regulates the expression of SLC22A4, a member of the carnitine/organic cation transporter family, which mediates the active uptake of imatinib into chronic myeloid leukemia cells. HPLC assay confirms that intracellular accumulation of imatinib is accompanied by upregulation of SLC22A4 through SOS1 inhibition in both sensitive and resistant chronic myeloid leukemia cells. BAY-293, an inhibitor of SOS1/Ras, was found to depress proliferation and colony formation in chronic myeloid leukemia cells with resistance and BCR-ABL independence. Altogether these findings indicate that targeting SOS1 inhibition promotes imatinib sensitivity and overcomes resistance with BCR-ABL independence by SLC22A4-mediated uptake transport.

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Long non-coding RNA LINC01268 promotes cell growth and inhibits cell apoptosis by modulating miR-217/SOS1 axis in acute myeloid leukemia

Cited by 12 publications

References 28 publications

Plasma-derived exosomal long noncoding RNAs of pancreatic cancer patients as novel blood-based biomarkers of disease

Plasma-derived exosomal long noncoding RNAs of pancreatic cancer patients as novel blood-based biomarkers of disease

Increased Plasma Levels of lncRNAs LINC01268, GAS5 and MALAT1 Correlate with Negative Prognostic Factors in Myelofibrosis

Targeting SOS1 overcomes imatinib resistance with BCR-ABL independence through uptake transporter SLC22A4 in CML

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