LncRNA KCNQ1OT1 activated by c-Myc promotes cell proliferation via interacting with FUS to stabilize MAP3K1 in acute promyelocytic leukemia

Tang, Doudou; Luo, Yujiao; Jiang, Yafeng; Hu, Piao; Peng, Hongling; Wu, Shangjie; Zhang, Guangsen; Wang, Yewei

doi:10.1038/s41419-021-04080-1

Cited by 15 publications

(7 citation statements)

References 54 publications

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“…According to the literature, lncRNA KCNQ1OT1 has also been proven to be involved in the progression of multiple diseases, such as osteolysis ( 47 ), fracture healing ( 48 ), myocardial ischemia/reperfusion injury ( 49 ), atrial fibrillation ( 50 ), and diabetic cardiomyopathy ( 51 ). Furthermore, research has shown that lncRNA KCNQ1OT1 is also related to the progression of acute promyelocytic leukemia ( 52 ), ovarian cancer ( 17 ), bladder cancer ( 53 ), and NSCLC ( 18 ). Moreover, studies demonstrated that lncRNA KCNQ1OT1 was involved in oxaliplatin-resistant colon cancer ( 16 ), methotrexate-resistant colorectal cancer ( 54 ), and cisplatin-resistant tongue cancer ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

LncRNA KCNQ1OT1 enhances the radioresistance of lung squamous cell carcinoma by targeting the miR-491-5p/TPX2-RNF2 axis

Liu¹,

Mi²,

Guan³

et al. 2022

J Thorac Dis

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Background: Lung cancer, especially lung squamous cell carcinoma (LUSC), is one of the most common malignant tumors worldwide. Currently, radiosensitization research is a vital direction for the improvement of LUSC therapy. Long non-coding RNAs (lncRNAs) can be novel biomarkers due to their multiple functions in cancers. However, the function and mechanism of lncRNA KCNQ1OT1 in the radioresistance of LUSC remain to be elucidated. Methods:The clonogenic assay was employed to determine the radioresistance of SK-MES-1R and NCI-H226R cells. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot were conducted for the detection of gene expression. Cell proliferation was determined by the methyl thiazolyl tetrazolium (MTT) assay, colony formation assay, and 5-ethynyl-2'-deoxyuridine (EdU) staining, and cell apoptosis was assessed by flow cytometry. The relationships between genes were also evaluated by applying the luciferase reporter and radioimmunoprecipitation (RIP) assays.Results: Radioresistant LUSC cells (SK-MES-1R and NCI-H226R) had strong resistance to X-ray irradiation, and lncRNA KCNQ1OT1 was highly expressed in SK-MES-1R and NCI-H226R cells.Moreover, knockdown of lncRNA KCNQ1OT1 prominently suppressed proliferation, attenuated radioresistance, and accelerated the apoptosis of SK-MES-1R and NCI-H226R cells. More importantly, we verified that miR-491-5p was a regulatory target of lncRNA KCNQ1OT1, and Xenopus kinesin-like protein 2 (TPX2) and RING finger protein 2 (RNF2) were the target genes of miR-491-5p. The rescue experiment results also demonstrated that miR-491-5p was involved in the inhibition of cell proliferation and the downregulation of TPX2 and RNF2 expression mediated by lncRNA KCNQ1OT1 knockdown in SK-MES-1R and NCI-H226R cells.Conclusions: LncRNA KCNQ1OT1 was associated with the radioresistance of radioresistant LUSC cells, and the lncRNA KCNQ1OT1/miR-491-5p/TPX2-RNF2 axis might be used as a therapeutic target to enhance the radiosensitivity of radioresistant LUSC cells.

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Section: Discussionmentioning

confidence: 99%

LncRNA KCNQ1OT1 enhances the radioresistance of lung squamous cell carcinoma by targeting the miR-491-5p/TPX2-RNF2 axis

Liu¹,

Mi²,

Guan³

et al. 2022

J Thorac Dis

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“…In some of children who suffer from this disease, embryonal tumors also point to the role of KCNQ1OT1 in cancer development. [10] As a matter of fact, recent studies have identified increased KCNQ1OT1 expression in retinoblastoma, acute promyelocytic leukemia, [10] bladder, [11] ovarian, [12] and non-small cell lung cancer (NSCLC). [13] However, no study has investigated the expression of KCNQ1OT1 in thyroid cancer.…”

Section: Introductionmentioning

confidence: 99%

Upregulation and the clinical significance of KCNQ1OT1 and HAGLROS lncRNAs in papillary thyroid cancer: An observational study

et al. 2023

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Long noncoding RNAs (lncRNAs) play an important role in regulating gene expression. Changes in their expression have been associated with many types of cancer, including thyroid cancer. This study aimed to investigate how changes in the expression of potassium voltage-gated channel subfamily Q member 1 opposite strand/antisense transcript 1 (KCNQ1OT1) and HAGLR opposite strand lncRNA (HAGLROS) lncRNAs correlate with the development and clinicopathological characteristics of papillary thyroid cancer (PTC). Reverse transcription-quantitative polymerase chain reaction was used to investigate the expression of lncRNAs in both tumor and adjacent normal thyroid tissue samples of the patients. Expressions of KCNQ1OT1 and HAGLROS were upregulated in the patients tumor samples compared to the adjacent normal thyroid samples. KCNQ1OT1 expression was linked to microcarcinoma and gender, while HAGLROS expression was linked to microcarcinoma and tumor size. When only microcarcinoma samples were evaluated, KCNQ1OT1 expression was higher in tumor tissues compared to normal tissues; however, no significant difference was observed in HAGLROS expression. Our data suggests that high expressions of KCNQ1OT1 and HAGLROS might contribute to the development of PTC and disease progression, and both lncRNAs may be potential therapeutic targets in PTC patients.

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“…For instance, lncRNA KCNQ1OT1 contributes to the development of acute myeloid leukemia by interacting with FUS to enhance the stability of MAP3K1 mRNA. 11 Lin-28 homologue B (LIN28B) is an RBP, and aberrant high expression of LIN28B in LPS-exposed cardiomyocytes can accelerate septic cardiomyopathy development via increasing PDCD4 mRNA stability. 12 Interestingly, the StarBase database predicted that CDKN2B-AS1 could bind to LIN28B.…”

Section: Introductionmentioning

confidence: 99%

“…LncRNAs can affect the stability of mRNAs via the interaction with RNA binding proteins (RBPs). For instance, lncRNA KCNQ1OT1 contributes to the development of acute myeloid leukemia by interacting with FUS to enhance the stability of MAP3K1 mRNA 11 . Lin‐28 homologue B (LIN28B) is an RBP, and aberrant high expression of LIN28B in LPS‐exposed cardiomyocytes can accelerate septic cardiomyopathy development via increasing PDCD4 mRNA stability 12 .…”

Section: Introductionmentioning

confidence: 99%

LncRNA CDKN2B‐AS1 interacts with LIN28B to exacerbate sepsis‐induced acute lung injury by inducing HIF‐1α/NLRP3‐mediated pyroptosis

Miao

2023

The Kaohsiung J of Med Scie

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Sepsis‐associated acute lung injury (ALI) is a life‐threatening condition in intensive care units with high mortality. LncRNAs have been confirmed to participate in the underlying pathogenesis of septic ALI. This study investigated the biological functions of lncRNA CDKN2B‐AS1 in septic ALI and its potential mechanism.BEAS‐2B cells were challenged with lipopolysaccharide (LPS) and mice were subjected to caecal ligation and puncture (CLP) to induce septic ALI in vitro and in vivo. The expression levels of CDKN2B‐AS1, LIN28B, HIF‐1α, and pyroptosis‐related molecules were assessed by qRT–PCR or Western blotting. The production of IL‐1β and IL‐18 was detected by ELISA. BEAS‐2B cell pyroptosis was examined by flow cytometry. The interaction between LIN28B and CDKN2B‐AS1/HIF‐1α was validated by RIP and RNA pull‐down assays. Colocalization of CDKN2B‐AS1 and LIN28B was observed by FISH. ALI was determined by HE staining, the lung wet‐to‐dry (W/D) weight ratio, inflammatory cell numbers, and total protein concentration in bronchoalveolar lavage fluid (BALF). Caspase‐1 expression in the lung tissues was examined by immunohistochemical staining.CDKN2B‐AS1 was upregulated in BEAS‐2B cells after LPS stimulation. CDKN2B‐AS1 knockdown inhibited pyroptosis in LPS‐exposed BEAS‐2B cells in vitro and the lung tissues of septic mice in vivo. Mechanistically, CDKN2B‐AS1 interacted with LIN28B to enhance HIF‐1α stability. Rescue experiments showed that HIF‐1α overexpression counteracted the inhibitory effect of sh‐CDKN2B‐AS1 on LPS‐induced pyroptosis. CDKN2B‐AS1 bound to LIN28B to trigger NLRP3‐mediated pyroptosis by stabilizing HIF‐1α, which promoted sepsis‐induced ALI. CDKN2B‐AS1 might be a novel therapeutic target for this disease.

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LncRNA KCNQ1OT1 activated by c-Myc promotes cell proliferation via interacting with FUS to stabilize MAP3K1 in acute promyelocytic leukemia

Cited by 15 publications

References 54 publications

LncRNA KCNQ1OT1 enhances the radioresistance of lung squamous cell carcinoma by targeting the miR-491-5p/TPX2-RNF2 axis

LncRNA KCNQ1OT1 enhances the radioresistance of lung squamous cell carcinoma by targeting the miR-491-5p/TPX2-RNF2 axis

Upregulation and the clinical significance of KCNQ1OT1 and HAGLROS lncRNAs in papillary thyroid cancer: An observational study

LncRNA CDKN2B‐AS1 interacts with LIN28B to exacerbate sepsis‐induced acute lung injury by inducing HIF‐1α/NLRP3‐mediated pyroptosis

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