LncRNA KCNQ1OT1 contributes to the progression and chemoresistance in acute myeloid leukemia by modulating Tspan3 through suppressing miR-193a-3p

Sun, Huifang; Sun, Yongfa; Chen, Qing; Xu, Zhaoying

doi:10.1016/j.lfs.2019.117161

Cited by 41 publications

(25 citation statements)

References 29 publications

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“…In a search for a potential therapy target for SCLC, lncRNAs have considerable great attention as oncogenes or tumor suppressors due to their ability to regulate cell proliferation, migration, invasion, and chemoresistance. Numerous studies have illustrated that a newly identified lncRNA, KCNQ1OT1, facilitates the progression and metastasis of non-small cell lung, breast, bladder, and colorectal cancer (20)(21)(22)(23), while inducing chemoresistance of hepatocellular carcinoma and acute myeloid leukemia (24,25). In the current study, microarray analysis of lncRNA expression profiles indicated that KCNQ1OT1 is involved in SCLC chemoresistance.…”

Section: Discussionmentioning

confidence: 51%

KCNQ1OT1 lncRNA affects the proliferation, apoptosis, and chemoresistance of small cell lung cancer cells via the JAK2/ STAT3 axis

Zhu¹,

Shen²,

Chen³

et al. 2021

Ann Transl Med

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Background: Small cell lung cancer (SCLC) is a devastating and aggressive neuroendocrine carcinoma characterized by high cellular proliferation and early metastatic spread. Numerous studies have demonstrated that long noncoding RNAs (lncRNAs) can regulate tumor generation and development, including in SCLC.The current study aimed to assess the effect of the lncRNA, KCNQ1OT1, on the proliferation, apoptosis, and chemoresistance of SCLC and the potential underlying molecular mechanism.Methods: Matched chemo-resistant and sensitive cells were applied to RNA isolation and followed by expression profiling by microarray analysis and subsequent quantitative polymerase chain reaction (qPCR) validation. Cell viability and apoptosis were determined by Cell Counting Kit-8 and flow cytometry to examine the chemoresistance and apoptosis of KCNQ1OT1 knockdown with lentivirus-mediated RNA interference. Furthermore, cell proliferation was studied by colony formation, and invasion and migration were tested by Transwell cell invasion and wound-healing assays, respectively. A tumor xenograft model was established to determine the role of KCNQ1OT1 in tumor growth and chemoresistance in response to KCNQ1OT1 knockdown in vivo. Western blot analysis, qPCR, and immunohistochemistry were used to detect the levels of messenger RNA (mRNA) Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway-related markers.Results: Higher expression of KCNQ1OT1 was detected in SCLC chemo-resistant verso chemo-sensitive cells. Knockdown of KCNQ1OT1 inhibited SCLC cell viability and cloning ability, hindered cell migration and invasion, induced apoptosis in vitro, and suppressed tumor growth and chemoresistance in vivo, by activating the JAK2/STAT3 signaling pathway.Conclusions: This is the first study to indicate that lncRNA KCNQ1OT1 promotes cell proliferation and invasion, and prevents apoptosis of SCLC by activating the JAK2/STAT3 pathway.

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Section: Discussionmentioning

confidence: 51%

KCNQ1OT1 lncRNA affects the proliferation, apoptosis, and chemoresistance of small cell lung cancer cells via the JAK2/ STAT3 axis

Zhu¹,

Shen²,

Chen³

et al. 2021

Ann Transl Med

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“…Recently, lncRNAs have been demonstrated to sponge miRNAs and therefore facilitate tumor development in numerous cancers, including AML. For example, previous research manifested that lncRNA KCNQ1OT1 contributed to the progression of AML by sponging miR-193a-3p [ 22 ]. In this regard, we wanted to know whether there was an interaction between TPTEP1 and miR-1303 in AML cells.…”

Section: Resultsmentioning

confidence: 99%

The mutual regulatory loop between TPTEP1 and miR-1303 in leukemogenesis of acute myeloid leukemia

Zhao

2021

Cancer Cell Int

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Background Non-coding RNAs (ncRNAs) have been identified as key regulators during the pathogenesis and development of cancers. However, most of ncRNAs have never been explored in acute myeloid leukemia (AML). Methods Gene expression was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Functional assays were performed to assess the cellular processes in AML cells. The relationship between genes was verified by means of a series of mechanism assays. Results Transmembrane phosphatase with tensin homology pseudogene 1 (TPTEP1) was notably downregulated in AML cells, and functionally acted as a proliferation-inhibitor. Additionally, TPTEP1 suppressed AML cell growth by inactivating c-Jun N-terminal kinase (JNK)/c-JUN signaling pathway. MicroRNA (MiR)-1303, as an oncogene, was predicted and validated as a target of c-JUN in AML cells. Also, TPTEP1 interacted with miR-1303 and they were mutually silenced by each other in AML cells. Furthermore, the effect of TPTEP1 overexpression on AML cell proliferation was counteracted under miR-1303 upregulation. Conclusion Our findings unmasked a feedback loop of TPTEP1/JNK/c-JUN/miR-1303 axis in AML cells, suggesting TPTEP1 and miR-1303 as potential targets for developing therapeutic strategies for AML patients.

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“…29 KCNQ1OT1 contributes to the development and chemoresistance in AML by modulating Tspan3 level. 30 High levels of SNHG3 predict a poor outcome for AML, and downregulation of SNHG3 has been identified to effectively suppress cell growth of AML cells. 31 RAET1K has been only studied in hepatocellular carcinoma, 10 and lung adenocarcinoma, 11 so we explored the potential role of RAET1K in AML.…”

Section: Discussionmentioning

confidence: 99%

lncRNA RAET1K Promotes the Progression of Acute Myeloid Leukemia by Targeting miR-503-5p/INPP4B Axis

Li¹,

Wan²,

Li³

et al. 2021

OTT

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Background: Although long non-coding RNA (lncRNA) RAET1K has been observed to be abnormally expressed in patients with various cancers, its role and molecular mechanism in acute myeloid leukemia (AML) remain unclear. Methods: The expression of RAET1K and miR-503-5p in bone marrow tissues and cell lines was detected by qRT-PCR. Cell proliferation was evaluated by cell counting kit-8 and 5-ethynyl-20-deoxyuridine (EdU) staining assay. Cell invasion and migration were detected by transwell assay. Cell apoptosis was evaluated by flow cytometry. The relationship between RAET1K and miR-503-5p, as well as miR-503-5p and INPP4B, was determined by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. In addition, the tumorigenesis of leukemia cells was evaluated by using a xenograft mouse model in vivo. Results: RAET1K was significantly upregulated and miR-503-5p was markedly downregulated in bone marrow tissues and cell lines (HL-60 and THP-1). Silencing of RAET1K (si-RAET1K) and overexpression of miR-503-5p inhibited cell proliferation, migration, and invasion but promoted apoptosis of HL-60 and THP-1 cells. RAET1K functioned as a sponge of miR-503-5p, and miR-503-5p inhibitor obviously attenuated the effect of si-RAET1K on AML progression in vitro. INPP4B was identified as a target of miR-503-5p, and INPP4B overexpression obviously reversed the effect of miR-503-5p mimics on cell proliferation, migration, invasion, and apoptosis of HL-60 and THP-1 cells in vitro. Knockdown of RAET1K effectively inhibited the tumorigenesis of leukemia cells in vivo. Conclusion:Our results demonstrated that RAET1K/miR-503-5p/INPP4B axis contributed to AML progression, suggesting that RAET1K might be a potential target for the treatment of AML.

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LncRNA KCNQ1OT1 contributes to the progression and chemoresistance in acute myeloid leukemia by modulating Tspan3 through suppressing miR-193a-3p

Cited by 41 publications

References 29 publications

KCNQ1OT1 lncRNA affects the proliferation, apoptosis, and chemoresistance of small cell lung cancer cells via the JAK2/ STAT3 axis

KCNQ1OT1 lncRNA affects the proliferation, apoptosis, and chemoresistance of small cell lung cancer cells via the JAK2/ STAT3 axis

The mutual regulatory loop between TPTEP1 and miR-1303 in leukemogenesis of acute myeloid leukemia

lncRNA RAET1K Promotes the Progression of Acute Myeloid Leukemia by Targeting miR-503-5p/INPP4B Axis

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