Long noncoding RNA NEAT1‐modulated miR‐506 regulates gastric cancer development through targeting STAT3

BackgroundGlioma stem cells (GSCs) are glioma cells with stemness and are responsible for a variety of malignant behaviors of glioma. Evidence has shown that signals from tumor microenvironment (TME) enhance stemness of glioma cells, but the identity of the signaling molecules and underlying mechanisms have been incompletely elucidated.MethodsHuman samples and glioma cell lines were cultured in vitro to determine the effects of viral infection by sphere formation, qRT-PCR, Western blot, FACS and immunofluorescence; for in vivo analysis, mice subcutaneous tumor model was carried; while bioinformatics analysis and qRT-PCR were applied for further mechanistic studies.ResultsIn this study, we show that infection of patient-derived glioma cells with adenovirus (ADV) increases the formation of tumor spheres. ADV infection upregulated stem cell markers, and the resultant tumor spheres held the capacities of self-renewal and multi-lineage differentiation, and had stronger potential to form xenograft tumors in immune-compromised mice. ADV promoted GSC formation likely via TLR9, because TLR9 was upregulated after ADV infection, and knockdown of TLR9 reduced ADV-induced GSCs. Consistently, MYD88, as well as total STAT3 and phosphorylated (p-)STAT3, were also upregulated in ADV-induced GSCs. Knockdown of MYD88 or pharmaceutical inhibition of STAT3 attenuated stemness of ADV-induced GSCs. Moreover, we found that ADV infection upregulated lncRNA NEAT1, which is downstream to TLRs and play important roles in cancer stem cells via multiple mechanisms including strengthening STAT3 signaling. Indeed, knockdown of NEAT1 impaired stemness of ADV-induced GSCs. Lastly, we show that HMGB1, a damage associated molecular pattern (DAMP) that also triggers TLR signaling, upregulated stemness markers in glioma cells.ConclusionsIn summary, our data indicate that ADV, which has been developed as vectors for gene therapy and oncolytic virus, promotes the formation of GSCs via TLR9/NEAT1/STAT3 signaling.

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“…These results, in combination with literatures, suggested that NEAT1 is downstream to TLR9-MYD88 and regulates STAT3 46,[48][49][50] .…”

Section: Neat1 Is Associated With Activation Of Tlr-stat Pathway In Gsupporting

confidence: 81%

Adenovirus infection promotes the formation of glioma stem cells by glioblastoma cells through the TLR9/NEAT1/STAT3 pathway

Zang

Zheng

Cao

et al. 2020

Preprint

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“…NEAT1, located at on chromosome 11q13.1, functions as a "miRNA sponge" to regulate gene expression and takes part in the progression of multiple cancers, such as breast cancer, prostate cancer, non-small-cell lung cancer, and gastric cancer (Chakravarty et al, 2014;Choudhry et al, 2015;Qi et al, 2018;Tan et al, 2018). NEAT1 is of two types: NEAT1_1 and NEAT1_2 (Clemson et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

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

Chen

Zhang

2018

Cell Biology International

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Radioresistance is a major obstacle in hepatocellular carcinoma (HCC) radiotherapy. Aberrant expression of long non-coding RNA (lncRNA) has been postulated to be implicated in the development of HCC radioresistance. We investigated the role of lncRNA nuclear enriched abundant transcript 1_2 (NEAT1_2) in radioresistance of HCC and its molecular mechanism in this study. We found that NEAT1_2 and WEE1 were upregulated, and miR-101-3p was downregulated in HCC tissues, as well as HCC cell lines. Downregulation of WEE1 sensitized the radiosensitivity of HCC cells, as evidenced by decreased survival fractions of Huh7 and PLC5 cells and increased percentage of apoptotic cells. Also, knockdown of NEAT1_2 exerted a reinforcing effect on the radiosensitivity of HCC cells. In addition, WEE1 was confirmed as a direct target of miR-101-3p. Upregulation of miR-101-3p obviously decreased the mRNA and protein levels of WEE1 compared with that in the miR-NC group, while transfection of anta-miR-101-3p presented the opposite effects. In parallel, NEAT1_2 was identified to interact with miR-101-3p, and NEAT1_2 upregulated the expression of WEE1 in Huh7 cells through sponging miR-101-3p. Besides, the reinforcing effect of NEAT1_2 silencing could be attenuated by downregulation of miR-101-3p. To conclude, our results support the concept that downregulation of lncRNA NEAT1_2 radiosensitizes hepatocellular carcinoma cells through regulation of miR-101-3p/WEE1 axis.

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“…[22][23][24] For instance, Gong et al proved that miR-506 inhibited cervical cancer cell proliferation both in vitro and in vivo. [22][23][24] For instance, Gong et al proved that miR-506 inhibited cervical cancer cell proliferation both in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA DQ786243 interacts with miR‐506 and promotes progression of ovarian cancer through targeting cAMP responsive element binding protein 1

Yan

Silva

et al. 2018

J of Cellular Biochemistry

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Long noncoding RNAs (lncRNAs) have been reported to be abnormally expressed in several cancers and associated with the proliferation of cancer cells. The objective of this study was to investigate the role and the underlying mechanisms of DQ786243 in ovarian cancer. In the current study, DQ786243 was specifically upregulated in ovarian cancer tissues and cell lines. Knockdown of DQ786243 inhibited the ability of cell migration, invasion, proliferation, colony formation and wound healing, whereas promoted cell apoptosis and induced G0/G1 cell cycle arresting. By using online tools and mechanistic analysis, we demonstrated that DQ786243 could directly bind to microRNA-506 (miR-506) and downregulate its expression. Moreover, DQ786243 reversed the inhibitory effect of miR-506 on the growth of ovarian cancer cells, which might be involved in the derepression of cAMP responsive element binding protein 1 (CREB1) expression. Further investigation into the mechanisms showed that knockdown of DQ786243 inhibited the epithelial to mesenchymal transition (EMT) process in ovarian cancer cells. Finally, xenograft experiments further confirmed that knockdown of DQ786243 notably suppressed the proliferation and EMT process in vivo. Taken together, our study showed for the first time that DQ786243 interacted with miR-506 and promoted progression of ovarian cancer via targeting CREB1 in ovarian cancer. The results might help to probe the feasibility of lncRNA-directed therapy for this deadly disease.

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Long noncoding RNA NEAT1‐modulated miR‐506 regulates gastric cancer development through targeting STAT3

Cited by 58 publications

References 41 publications

Adenovirus infection promotes the formation of glioma stem cells by glioblastoma cells through the TLR9/NEAT1/STAT3 pathway

Adenovirus infection promotes the formation of glioma stem cells by glioblastoma cells through the TLR9/NEAT1/STAT3 pathway

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

Long noncoding RNA DQ786243 interacts with miR‐506 and promotes progression of ovarian cancer through targeting cAMP responsive element binding protein 1

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