lncRNA NBAT1 Inhibits Cell Metastasis and Promotes Apoptosis in Endometrial Cancer by Sponging miR-21-5p to Regulate PTEN

Tian, Chao; Su, Jing; Ma, Zhiyong; Wu, Yang Chang; Ma, Hongyun

doi:10.1155/2022/9304392

Cited by 12 publications

(6 citation statements)

References 44 publications

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“…Increasing evidence manifests that miR-21-5p/PTEN axis is involved in carcinogenesis [31][32][33]. We found that miR-21-5p mimics could inhibit the luciferase activity of WT PTEN 3' UTR, but exhibited no effect on that of the Mut PTEN 3'UTR compared to the miR-NC group in 95D and H1299 cells (Fig.…”

Section: Hnrnpa2b1 Mediated Lncrna Meg3 To Regulate Mir-21-5p/pten Axismentioning

confidence: 64%

HNRNPA2B1-mediated m6A modification of lncRNA MEG3 facilitates tumorigenesis and metastasis of non-small cell lung cancer by regulating miR-21-5p/PTEN axis

Li¹,

Gong²,

Xiang³

et al. 2023

Preprint

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Background Increasing data imply that heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) as a nuclear N6-methyladenosine (m6A) reader acts crucial roles in cancer progression. However, the role and underlying mechanism by which HNRNPA2B1-mediated m6A modification of lncRNA contributes to non-small cell lung cancer (NSCLC) remain undocumented. Methods The association of HNRNPA2B1 expression with the clinicopathological characteristics and prognosis in patients with NSCLC was determined by qRT-PCR, Western blot, immunohistochemistry and public datasets. The role of HNRNPA2B1 in NSCLC cells was assessed by the in vitro experiments and in vivo tumorigenesis and metastasis models. The m6A-lncRNA epi-transcriptomic microarray was employed to screen HNRNPA2B1-mediated m6A modification of lncRNAs, which were verified by methylated RNA immunoprecipitation (Me-RIP), RT-qPCR and rescue experiments in NSCLC cells. lncRNA MEG3-specific binding with miR-21-5p was validated by luciferase gene report and RIP assays. The effects of HNRNPA2B1 and (or) lncRNA MEG3 on miR-21-5p/PTEN/PI3K/AKT signaling were examined by RT-qPCR and Western blot analyses. Results We found that upregulation of HNRNPA2B1 was associated with distant metastasis and represented an independent prognostic factor for poor survival in patients with NSCLC. Knockdown of HNRNPA2B1 impaired cell proliferation and metastasis of NSCLC cells in vitro and in vivo, whereas ectopic expression of HNRNPA2B1 possessed the opposite effects. Mechanical investigations revealed that lncRNA MEG3 was identified as an m6A target of HNRNPA2B1 and inhibition of HNRNPA2B1 decreased the m6A level of lncRNA MEG3 but increased its expression levels. Furthermore, lncRNA MEG3 acted as a sponge of miR-21-5p, and knockdown of lncRNA MEG3 attenuated sh-HNRNPA2B1-caused inhibitory effects on cell colony formation and invasion. Elevated expression of miR-21-5p indicated poor survival in patients with NSCLC and inhibition of miR-21-5p counteracted si-MEG3-induced PTEN downregulation and PI3K/AKT signaling activation in NSCLC cells. Conclusions Our findings uncover that HNRNPA2B1-mediated m6A modification of lncRNA MEG3 promotes tumorigenesis and metastasis of NSCLC cells by regulating miR-21-5p/PTEN axis.

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Section: Hnrnpa2b1 Mediated Lncrna Meg3 To Regulate Mir-21-5p/pten Axismentioning

confidence: 64%

HNRNPA2B1-mediated m6A modification of lncRNA MEG3 facilitates tumorigenesis and metastasis of non-small cell lung cancer by regulating miR-21-5p/PTEN axis

Li¹,

Gong²,

Xiang³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Increasing evidence manifests that miR-21-5p/PTEN axis is involved in carcinogenesis [ 31 – 33 ]. We found that miR-21-5p mimics could inhibit the luciferase activity of WT PTEN 3’ UTR, but exhibited no effect on that of the Mut PTEN 3’UTR compared to the miR-NC group in 95D and H1299 cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

HNRNPA2B1-mediated m6A modification of lncRNA MEG3 facilitates tumorigenesis and metastasis of non-small cell lung cancer by regulating miR-21-5p/PTEN axis

Li¹,

Gong²,

Xiang³

et al. 2023

J Transl Med

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Background Accumulating data indicate that N6-methyladenosine (m6A) RNA methylation and lncRNA deregulation act crucial roles in cancer progression. Heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) as an m6A “reader” has been reported to be an oncogene in multiple malignancies. We herein aimed to elucidate the role and underlying mechanism by which HNRNPA2B1-mediated m6A modification of lncRNAs contributes to non-small cell lung cancer (NSCLC). Methods The expression levels of HNRNPA2B1 and their association with the clinicopathological characteristics and prognosis in NSCLC were determined by RT-qPCR, Western blot, immunohistochemistry and TCGA dataset. Then, the role of HNRNPA2B1 in NSCLC cells was assessed by in vitro functional experiments and in vivo tumorigenesis and lung metastasis models. HNRNPA2B1-mediated m6A modification of lncRNAs was screened by m6A-lncRNA epi-transcriptomic microarray and verified by methylated RNA immunoprecipitation (Me-RIP). The lncRNA MEG3-specific binding with miR-21-5p was evaluated by luciferase gene report and RIP assays. The effects of HNRNPA2B1 and (or) lncRNA MEG3 on miR-21-5p/PTEN/PI3K/AKT signaling were examined by RT-qPCR and Western blot analyses. Results We found that upregulation of HNRNPA2B1 was associated with distant metastasis and poor survival, representing an independent prognostic factor in patients with NSCLC. Knockdown of HNRNPA2B1 impaired cell proliferation and metastasis in vitro and in vivo, whereas ectopic expression of HNRNPA2B1 possessed the opposite effects. Mechanical investigations revealed that lncRNA MEG3 was an m6A target of HNRNPA2B1 and inhibition of HNRNPA2B1 decreased MEG3 m6A levels but increased its mRNA levels. Furthermore, lncRNA MEG3 could act as a sponge of miR-21-5p to upregulate PTEN and inactivate PI3K/AKT signaling, leading to the suppression of cell proliferation and invasion. Low expression of lncRNA MEG3 or elevated expression of miR-21-5p indicated poor survival in patients with NSCLC. Conclusions Our findings uncover that HNRNPA2B1-mediated m6A modification of lncRNA MEG3 promotes tumorigenesis and metastasis of NSCLC cells by regulating miR-21-5p/PTEN axis and may provide a therapeutic target for NSCLC.

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“…The study confirmed through cellular experiments that NBTA1 was targeted to bind to miR-21-5p, and overexpression of miR-21-5p not only promoted EC proliferation and invasion but also inhibited apoptosis. It also had the effect of blocking NBTA1 on EC cells [ 17 ]. MiR-21-5p has also been studied in other tumors, e.g., peritoneal cancer [ 18 ], lung cancer [ 19 ], colorectal cancer [ 20 ], breast cancer [ 21 ], and ovarian cancer [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Absolute Quantification of Selected microRNAs Expression in Endometrial Cancer by Digital PCR

Bogaczyk,

Potocka,

Paszek

et al. 2024

IJMS

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MicroRNAs (miRNA) are involved in the process of carcinogenesis, including the development of endometrial cancer (EC). This study aimed to investigate the association between the expression of three miRNAs (miR-21-5p, miR-205-5p, and miR-222-3p) in endometrial cancer tissues. In addition, the stability of expression of SNORD48 and U6, which were initially planned to be used as reference miRNAs for normalization, was investigated. Endometrial tissue was obtained from 111 patients with EC during hysterectomy and from 19 patients undergoing surgery for uterine fibroids or pelvic organ prolapse as a control group without neoplastic changes. Our study was based on calculations made with a digital PCR method (Qiagen, Hilden, Germany) to measure the absolute expression. In the endometrial cancer tissue, miR-205-5p was upregulated, while miR-222-3p and SNORD48 were downregulated compared to the control group. We detected statistically significant correlation of miR-205-5p, U6, and SNORD48 expression with different histological grades; the expression of miR-205-5p increases with the histopathological grade advancement (intraepithelial neoplasia- EIN = 1590, G1 = 3367.2, G2 = 8067 and G3 = 20,360), while U6 and SNORD expression decreases from EIN to G2 and increases again in the G3 grade (U6: EIN = 19,032, G1 = 16,482.4, G2 = 13,642.4, G3 = 133,008; SNORD48: EIN = 97,088, G1 = 59,520, G2 = 43,544, G3 = 227,200). Our study suggests that upregulation of miR-205-5p and downregulation of miR-222-3p and SNORD48 may influence development of endometrial cancer. Moreover, miR-205-5p, U6, and SNORD48 expression changes may be associated with progression of endometrial cancer. The results also indicate that SNORD48 and U6, commonly used as internal references, may influence endometrial cancer development and progression; therefore, they should not be used as references. However, it is important to note that further research is required to understand their role in endometrial cancer.

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lncRNA NBAT1 Inhibits Cell Metastasis and Promotes Apoptosis in Endometrial Cancer by Sponging miR-21-5p to Regulate PTEN

Cited by 12 publications

References 44 publications

HNRNPA2B1-mediated m6A modification of lncRNA MEG3 facilitates tumorigenesis and metastasis of non-small cell lung cancer by regulating miR-21-5p/PTEN axis

HNRNPA2B1-mediated m6A modification of lncRNA MEG3 facilitates tumorigenesis and metastasis of non-small cell lung cancer by regulating miR-21-5p/PTEN axis

HNRNPA2B1-mediated m6A modification of lncRNA MEG3 facilitates tumorigenesis and metastasis of non-small cell lung cancer by regulating miR-21-5p/PTEN axis

Absolute Quantification of Selected microRNAs Expression in Endometrial Cancer by Digital PCR

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