Downregulation of lncRNA NEAT1_2 radiosensitizes hepatocellular carcinoma cells through regulation of miR‐101‐3p/WEE1 axis

Chen, Xin; Zhang, Nuobei

doi:10.1002/cbin.11077

Cited by 47 publications

(33 citation statements)

References 39 publications

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“…However, NEAT1 was also reported to interact with many other miRNAs. For example, NEAT1 was reported to sponge miR-101 in non-small cell lung cancer [34], papillary thyroid carcinoma [35], hepatocellular carcinoma [36] and breast cancer [11]. Besides, NEAT1 sponged miR-124 in neuroblastoma [37], retinoblastoma [38], Alzheimer's disease [38] and nasopharyngeal carcinoma [39].…”

Section: Discussionmentioning

confidence: 99%

STAT3-induced up-regulation of lncRNA NEAT1 as a ceRNA facilitates abdominal aortic aneurysm formation by elevating TULP3

et al. 2020

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Long noncoding RNAs (lncRNAs) were viewed as crucial participants in the pathogenesis of abdominal aortic aneurysm (AAA). LncRNA NEAT1 was recognized as an oncogenic gene in various diseases. However, its function and mechanism in AAA were not precisely documented. Here, we explored the functional role and molecular mechanism of NEAT1 in AAA. Functionally, the effect of NEAT1 on the proliferation was assessed by CCK-8 and EdU assay, while its impact on the apoptosis was evaluated through caspase-3/9 activity and TUNEL assays. As a result, we found that NEAT1 knockdown enhanced the proliferation and impaired the apoptosis of vascular smooth muscle cells (VSMCs). Reversely, overexpressed NEAT1 exerted anti-proliferation and pro-apoptosis effects in VSMCs. Mechanically, we found that STAT3 acted as a transcription factor and contributed to NEAT1 transcription by ChIP and luciferase reporter assays. In addition, NEAT1 was confirmed as a sponge of miR-4688 and thereby increase the expression of TULP3 in VSMCs via RIP assay and RNA pull-down assay. Rescue experiments indicted that TULP3 overexpressing countervailed the impact of NEAT1 depletion on AAA biological processes. Conclusively, lncRNA NEAT1 induced by STAT3 was identified as a ceRNA and facilitated AAA formation by targeting miR-4688/TULP3 axis.

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Section: Discussionmentioning

confidence: 99%

STAT3-induced up-regulation of lncRNA NEAT1 as a ceRNA facilitates abdominal aortic aneurysm formation by elevating TULP3

et al. 2020

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“…WEE1 was shown to be a direct target of miR-101-3p. NEAT1_2 was shown to up-regulate WEE1 through sponging by lncRNA miR-101-3p and down-regulation of lncRNA NEAT1_2, resulting in the radiosensitization of HCC cells [69]. PTEN deficiency was thought to be the leading cause of hyperactivation of the PI3K/Akt signaling pathway.…”

Section: Radiation-associated Mirnas In Hccmentioning

confidence: 99%

Radiosensitization of Hepatocellular Carcinoma through Targeting Radio-Associated MicroRNA

Chen

Yeh

et al. 2020

IJMS

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Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide. For patients who are resistant to monotherapy, multimodal therapy is a basic oncologic principle that incorporates surgery, radiotherapy (RT), and chemotherapy providing survival benefits for patients with most types of cancer. Although liver has low tolerance for radiation, high-precision RT for local HCC minimizes the likelihood of radiation-induced liver disease (RILD) in noncancerous liver tissue. RT have several therapeutic benefits, including the down-staging of tumors to make them resectable and repression of metastasis. The DNA damage response (DDR) is a cellular response to irradiation (IR), including DNA repair of injured cells and induction of programmed cell death, thereby resulting in maintenance of cell homeostasis. Molecules that block the activity of proteins in DDR pathways have been found to enhance radiotherapeutic effects. These molecules include antibodies, kinase inhibitors, siRNAs and miRNAs. MicroRNAs (miRNAs) are short non-coding regulatory RNAs binding to the 3 -untranslated regions (3 -UTR) of the messenger RNAs (mRNAs) of target genes, regulating their translation and expression of proteins. Thus, miRNAs and their target genes constitute complicated interactive networks, which interact with other molecules during carcinogenesis. Due to their promising roles in carcinogenesis, miRNAs were shown to be the potential factors that mediated radiosensitivity and optimized outcomes of the combination of systemic therapy and radiotherapy.

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“…WEE1 G2 checkpoint kinase (WEE1) is a tyrosine kinase that modulates G2/M checkpoints before mitosis in response to DNA damages . WEE1 is up‐regulated in multiple malignancies, such as liver cancer, nasopharyngeal carcinoma, and NSCLC, and is closely linked to poor efficacy of radiotherapy . It was reported that a WEE1 inhibitor (AZD1755) sensitized NSCLC cells, which carried a KRAS mutant, to radiotherapy .…”

Section: Introductionmentioning

confidence: 99%

“…It was reported that a WEE1 inhibitor (AZD1755) sensitized NSCLC cells, which carried a KRAS mutant, to radiotherapy . Additionally, studies have revealed that WEE1 can be negatively regulated by several miRNAs, such as miR‐101‐3p and miR‐503 …”

Section: Introductionmentioning

confidence: 99%

Quercetin radiosensitizes non‐small cell lung cancer cells through the regulation of miR‐16‐5p/WEE1 axis

et al. 2020

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Background Quercetin, a widely distributed bioflavonoid, plays a role in combating diverse human cancers including non‐small cell lung cancer (NSCLC). However, the role of quercetin in reversing the radioresistance of NSCLC cells and its underlying mechanism are far from being elucidated. Method Radiation‐resistant NSCLC cell lines were established. Quantitative real‐time PCR (qRT‐PCR) was used to detect the expression of miR‐16‐5p and WEE1 G2 checkpoint kinase (WEE1) mRNA in radiation‐resistant cells. After being treated with different concentrations of quercetin and different doses of X‐ray, cell proliferation and apoptosis were monitored by CCK‐8 assay, colony formation assay, and flow cytometry, respectively. Ultimately, the targeting relationship between miR‐16‐5p and WEE1 was verified via a dual fluorescent reporter gene assay. Results The expression of miR‐16‐5p was down‐regulated in radiation‐resistant cells, while the expression of WEE1 was up‐regulated. Quercetin enhanced the radiosensitivity of NSCLC cells in a dose‐ and time‐dependent manner. Furthermore, quercetin treatment increased the expression of miR‐16‐5p and decreased the expression of WEE1. The function of quercetin was reversed by miR‐16‐5p inhibitors or the transfection of WEE1 overexpressing plasmids. Conclusion In conclusion, quercetin enhanced the radiosensitivity of NSCLC cells via modulating the expression of miR‐16‐5p and WEE1.

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Downregulation of lncRNA NEAT1_2 radiosensitizes hepatocellular carcinoma cells through regulation of miR‐101‐3p/WEE1 axis

Cited by 47 publications

References 39 publications

STAT3-induced up-regulation of lncRNA NEAT1 as a ceRNA facilitates abdominal aortic aneurysm formation by elevating TULP3

STAT3-induced up-regulation of lncRNA NEAT1 as a ceRNA facilitates abdominal aortic aneurysm formation by elevating TULP3

Radiosensitization of Hepatocellular Carcinoma through Targeting Radio-Associated MicroRNA

Quercetin radiosensitizes non‐small cell lung cancer cells through the regulation of miR‐16‐5p/WEE1 axis

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