lincRNA‐p21 inhibits invasion and metastasis of hepatocellular carcinoma through Notch signaling‐induced epithelial–mesenchymal transition

Meng, Jia; Jiang, Li; Wang, Yadong; Huang, Jinzhao; Yu, Miao; Xue, Hao

doi:10.1111/hepr.12659

Cited by 65 publications

(56 citation statements)

References 36 publications

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“…Osteoblasts are implicated in the incidence and progression of osteoporosis [35]. Many lncRNAs are regulated by osteoblasts, including the lncRNA repertoire and lncRNA-p21 [36,37]. DLL3 is an upregulated gene of the Notch signaling pathway, which is also regulated by osteoblast activity [15,38,39].…”

Section: Figure 14mentioning

confidence: 99%

LncRNA LINC00311 Promotes the Proliferation and Differentiation of Osteoclasts in Osteoporotic Rats Through the Notch Signaling Pathway by Targeting DLL3

Wang¹,

Luo²,

Liu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Osteoporosis is a commonly occurring condition marked by a loss of bone density. Previous evidence has highlighted the roles played by microRNAs as potential treatment tools for the disease. At present, the influence of long non-coding RNAs (lncRNAs) on the progression of osteoporosis remains largely unclear. Thus, an investigation was conducted into the target relationship between LINC00311, which has been reported to be highly expressed in osteoporosis, and delta-like 3 (DLL3), which is involved in the Notch signaling pathway, in connection with a series of bioinformatic methods. An osteoporotic rat model was established by means of ovariectomy (OVX) to evaluate the influence exerted by DLL3-binding LINC00311 on osteoclasts through the Notch signaling pathway. Methods: Osteoclasts were extracted from osteoporotic rats and transfected with the LINC00311-vector, shRNA-LINC00311, Notch activator, or a combination of the Notch activator and LINC00311-vector. Western blotting and RT-qPCR techniques were applied to determine the expression levels of LINC00311, DLL3, Notch1, Notch2, Jagged1, Hes-1 and TRAP in tissues and cells, while cell activity was detected by MTT assay. The cell cycle as well as the rate of apoptosis was detected by flow cytometry. The successfully established osteoporotic rats were designated into the OVX-siRNA, OVX-LINC00311 and OVX-control groups to observe the effects of LINC00311 on the proliferation and differentiation of osteoclasts. Results: Cells transfected with the LINC00311-vector exhibited increased expression levels of Notch2 and TRPA as well as increased cell activity, while decreased expression levels of DLL3, Notch1, Jagged1 and Hes-1, along with a decreased cell apoptosis rate, were observed. The opposite tendencies of these parameters were observed in the cells treated with shRNA-LINC00311. A key observation was made when the Notch signaling pathway was activated, in that the cell activity was decreased while the rate of apoptosis increased. In comparison with the OVX-control group, the expression levels of LINC00311, Notch2 and TRAP as well as the positive expression rate of TRAP all exhibited reductions, while those of DLL3, Jagged1 and Notch1 were elevated in the OVX-siRNA group. Compared with those in the sham group, in the OVX-control and OVX-LINC00311 groups, LINC00311 and the expression levels of Notch2 and TRAP were increased; however, decreased levels of DLL3, Jagged1 and Notch1 were noted. Conclusions: Taken together, the key findings of the present study suggest that LINC00311 induces proliferation and inhibits apoptosis of osteoclasts via the regulation of the Notch signaling pathway by inhibiting DLL3 expression, ultimately demonstrating that LINC00311 and its target gene DLL3 may serve as independent factors in cases of osteoporosis.

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Section: Figure 14mentioning

confidence: 99%

LncRNA LINC00311 Promotes the Proliferation and Differentiation of Osteoclasts in Osteoporotic Rats Through the Notch Signaling Pathway by Targeting DLL3

Wang¹,

Luo²,

Liu³

et al. 2018

Cell Physiol Biochem

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“…Its expression has been shown to be downregulated in prostate cancer [258], NSCLC [374] and HCC [255]. LincRNA-p21 has been shown in HCC to inhibit EMT via Notch signalling [255], but it plays many other additional regulatory roles [254,257,373,375]. …”

Section: Lncrnas and Emt: The Main Playersmentioning

confidence: 99%

“…HOTAIR and ZFAS1 have both been found to promote Notch signalling, while, as already mentioned, lincRA-p21 inhibits Notch signalling [255,423,424]. PVT1 activates Hedgehog signalling through indirectly regulating methylation of PTCH1 via miR-152 [328], while lncRNA-HH also activates Hedgehog signalling to promote EMT, possibly via promoting expression of GAS1, an enhancer of Hedgehog signalling [231,358].…”

Section: Lncrnas In Signalling Pathways Governing Emtmentioning

confidence: 99%

Long Non-Coding RNAs: Key Regulators of Epithelial-Mesenchymal Transition, Tumour Drug Resistance and Cancer Stem Cells

Heery

Finn

Cuffe

et al. 2017

Cancers

163

140

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Epithelial mesenchymal transition (EMT), the adoption by epithelial cells of a mesenchymal-like phenotype, is a process co-opted by carcinoma cells in order to initiate invasion and metastasis. In addition, it is becoming clear that is instrumental to both the development of drug resistance by tumour cells and in the generation and maintenance of cancer stem cells. EMT is thus a pivotal process during tumour progression and poses a major barrier to the successful treatment of cancer. Non-coding RNAs (ncRNA) often utilize epigenetic programs to regulate both gene expression and chromatin structure. One type of ncRNA, called long non-coding RNAs (lncRNAs), has become increasingly recognized as being both highly dysregulated in cancer and to play a variety of different roles in tumourigenesis. Indeed, over the last few years, lncRNAs have rapidly emerged as key regulators of EMT in cancer. In this review, we discuss the lncRNAs that have been associated with the EMT process in cancer and the variety of molecular mechanisms and signalling pathways through which they regulate EMT, and finally discuss how these EMT-regulating lncRNAs impact on both anti-cancer drug resistance and the cancer stem cell phenotype.

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“…Mechanism study suggested that EMT-related protein E-cadherin, a tumor invasion suppressor in HCC, was identified as a putative gene target of miR-9 11. Besides, the previous study by the authors of this current paper showed that the expression of E-cadherin was upregulated by overexpression of lincRNA-p21 7. This has led to the speculation that lincRNA-p21 may regulate the expression of E-cadherin via mediating miR-9 expression, finally leading to the inhibition of HCC progression and development.…”

Section: Introductionmentioning

confidence: 60%

“…The most widely investigated lncRNAs in HCC include MALAT1, HOX antisense intergenic RNA H19, MEG3, MVIH and HULC 6. Besides, in the previous study, lincRNA-p21, a long intergenic noncoding RNA (lincRNA), was identified as an lincRNA that inhibits invasion and metastasis of HCC, and the underlying mechanism was found to be associated with the enhancement of epithelial–mesenchymal transition (EMT) 7. The aim of this study was to explore the further mechanism underlying the effects of lincRNA-p21 on EMT in HCC cells.…”

Section: Introductionmentioning

confidence: 93%

LincRNA-p21 inhibits invasion and metastasis of hepatocellular carcinoma through miR-9/E-cadherin cascade signaling pathway molecular mechanism

Ding

Peng

Shang

et al. 2017

OTT

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In the previous study, it was found that long intergenic noncoding RNA-p21 (lincRNA-p21) was downregulated in hepatocellular carcinoma (HCC) and lincRNA-p21 overexpression inhibited tumor invasion through inducing epithelial–mesenchymal transition. However, the underlying mechanism was not fully elaborated. In this study, lincRNA-p21 expression was measured in 12 paired HCC and nontumor adjacent normal tissues by quantitative real-time polymerase chain reaction. The effects of lincRNA-p21 on HCC cells were studied using lentivirus expressing lincRNA-p21 vector in vitro. The association between lincRNA-p21 level and miR-9 level was tested with the Spearman rank correlation. The effects of miR-9 on HCC cells were studied by using miR-9 inhibitor in vitro. Luciferase assay was used to validate the target of miR-9. The results showed that lincRNA-p21 was downregulated in human HCC tissues and cell lines. LincRNA-p21 overexpression significantly inhibited HCC cell migration and invasion in vitro. Besides, lincRNA-p21 negatively regulated miR-9 expression level, and miR-9 was upregulated in human HCC tissues and cells. MiR-9 knockdown inhibited HCC cell migration and invasion in vitro. Finally, the luciferase assay results showed that E-cadherin was a direct target of miR-9. The expression level of E-cadherin was found to be regulated by lincRNA-p21 and miR-9. Altogether, the results suggested that lincRNA-p21 inhibits migration and invasion of HCC cells through regulating miR-9-mediated E-cadherin cascade signaling pathway.

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lincRNA‐p21 inhibits invasion and metastasis of hepatocellular carcinoma through Notch signaling‐induced epithelial–mesenchymal transition

Abstract: lincRNA-p21 was downregulated in HCC and lincRNA-p21 overexpression contributed to the inhibition of tumor invasion through mediating Notch signaling induced EMT.

Cited by 65 publications

References 36 publications

LncRNA LINC00311 Promotes the Proliferation and Differentiation of Osteoclasts in Osteoporotic Rats Through the Notch Signaling Pathway by Targeting DLL3

LncRNA LINC00311 Promotes the Proliferation and Differentiation of Osteoclasts in Osteoporotic Rats Through the Notch Signaling Pathway by Targeting DLL3

Long Non-Coding RNAs: Key Regulators of Epithelial-Mesenchymal Transition, Tumour Drug Resistance and Cancer Stem Cells

LincRNA-p21 inhibits invasion and metastasis of hepatocellular carcinoma through miR-9/E-cadherin cascade signaling pathway molecular mechanism

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