LncRNA MALAT1 Promotes Cancer Metastasis in Osteosarcoma via Activation of the PI3K-Akt Signaling Pathway

Chen, Yong; Huang, Wending; Sun, Wei; Zheng, Biqiang; Wang, Chunmeng; Luo, Zhiguo; Wang, Jian; Yan, Wangjun

doi:10.1159/000495550

Cited by 98 publications

(63 citation statements)

References 22 publications

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“…In OS, MALAT1 modulates RET proto-oncogene expression by sponging miR-129-5p, increasing protein expression downstream of the RET-Akt pathway, and its expression was positively correlated with RET and negatively correlated with miR-129-5p in original OS and in xenografted tumor cells. This shows that MALAT1 act as oncogenic lncRNA in OS by regulating RET via miR-129-5p suppression, thereby activating the PI3K-Akt signaling pathway (112).…”

Section: Role Of Non-coding Rnasmentioning

confidence: 93%

Biology and pathogenesis of human osteosarcoma (Review)

Azevedo¹,

Fernandes

et al. 2019

Oncol Lett

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Osteosarcoma (OS) is a bone tumor of mesenchymal origin, most frequently occurring during the rapid growth phase of long bones, and usually located in the epiphyseal growth plates of the femur or the tibia. Its most common feature is genome disorganization, aneuploidy with chromosomal alterations, deregulation of tumor suppressor genes and of the cell cycle, and an absence of DNA repair. This suggests the involvement of surveillance failures, DNA repair or apoptosis control during osteogenesis, allowing the survival of cells which have undergone alterations during differentiation. Epigenetic events, including DNA methylation, histone modifications, nucleosome remodeling and expression of non-coding RNAs have been identified as possible risk factors for the tumor. It has been reported that p53 target genes or those genes that have their activity modulated by p53, in addition to other tumor suppressor genes, are silenced in OS-derived cell lines by hypermethylation of their promoters. In osteogenesis, osteoblasts are formed from pluripotent mesenchymal cells, with potential for self-renewal, proliferation and differentiation into various cell types. This involves complex signaling pathways and multiple factors. Any disturbance in this process can cause deregulation of the differentiation and proliferation of these cells, leading to the malignant phenotype. Therefore, the origin of OS seems to be multifactorial, involving the deregulation of differentiation of mesenchymal cells and tumor suppressor genes, activation of oncogenes, epigenetic events and the production of cytokines. Contents 1. Introduction 2. Biology of human OS 3. Role of differentiation of mesenchymal stem cells 4. Role of DNA changes 5. Role of deregulating the expression of tumor suppressor genes 6. Regulation of oncogene expression 7. Role of epigenetic mechanisms 8. Role of non-coding RNAs 9. Role of cytokines 10. Conclusion

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Section: Role Of Non-coding Rnasmentioning

confidence: 93%

Biology and pathogenesis of human osteosarcoma (Review)

Azevedo¹,

Fernandes

et al. 2019

Oncol Lett

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“…The new regulatory network may shed light on the mechanism of RB progression. There were evidences indicated that MALAT1 promoted tumor progression through phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway in non-small cell lung cancer [27] and osteosarcoma [28]. In the next exploration, we will focus on whether the MALAT1/miR-655-3p/ATAD2-induced RB progression was mediated by PI3K/AKT/mTOR signaling pathway.…”

Section: Discussionmentioning

confidence: 98%

Long non-coding RNA MALAT1 regulated ATAD2 to facilitate retinoblastoma progression by sponging miR-655-3p

Zhao¹,

Wang²,

Gao³

et al. 2020

Preprint

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Background: Long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was reported as an oncogene in many tumors including retinoblastoma (RB). This research mainly focused on the functions and mechanism of MALAT1 in RB.Methods: The levels of MALAT1, microRNA-655-3p (miR-655-3p), and ATPase family AAA domain containing 2 (ATAD2) in RB tissues and cells were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The cell viability and apoptotic rate were monitored via cell counting kit 8 (CCK8) assay and flow cytometry, respectively. The protein levels of p21, CyclinD1, B-cell lymphoma-2 (Bcl-2), cleaved-casp-3, E-cadherin, Ncadherin, Vimentin, and ATAD2 were detected by Western blot assay. Transwell assay was performed to estimate the abilities of migration and invasion. The interactions between miR-655-3p and MALAT1 or ATAD2 were predicted by starBase. Dual-luciferase reporter assay was constructed to verify these interactions. The mice model experiments were established to validate the effects of MALAT1 in vivo.Results: MALAT1and ATAD2 were significantly increased while the level of miR-655-3p was remarkably decreased in RB tissues and cells. MALAT1 knockdown inhibited cell proliferation, metastasis, and epithelial-mesenchymal transition (EMT) but promoted apoptosis via miR-655-3p in vitro, and blocked xenograft tumor growth in vivo. MALAT1 was validated to sponge miR-655-3p and ATAD2 was verified as a candidate of miR-655-3p. MiR-655-3p overexpression inhibited cell proliferation but promoted apoptosis by targeting ATAD2. MALAT1 silencing affected cell behaviors by regulating ATAD2. MALAT1 depletion down-regulated ATAD2 expression via miR-655-3p in RB cells.Conclusion: MALAT1 positively regulated ATAD2 to accelerate cell proliferation but retard apoptosis by sponging miR-655-3p in RB cells.

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“…Epigenetic regulation of miR-129-2 was demonstrated in glioma and lung cancer [25,26]. In contrast, however, miR-129 is also upregulated in several solid tumors and non-cancerous tissues from cancer patients with lymph node metastases [27][28][29].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-129-2-3p directly targets Wip1 to suppress the proliferation and invasion of intrahepatic cholangiocarcinoma

Chen¹,

Jiang²,

Fang³

et al. 2020

J. Cancer

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Accumulated studies showed that numerous microRNAs (miRNAs) were aberrantly expressed in human intrahepatic cholangiocarcinoma (ICC) and contributed to the tumorigenic processes. However, whether miR-129-2-3p is implicated in the ICC initiation and progression is still limited. Here, the results revealed that miR-129-2-3p expression was notably decreased in ICC tissues and cell lines, and that a low miR-129-2-3p expression was obviously associated with distant metastasis and clinical stage. Exogenous miR-129-2-3p expression evidently repressed the proliferative and invasive abilities of ICC cells. Mechanistic studies indicated that Wild-type p53-induced phosphatase 1 (Wip1) was a direct target gene for miR-129-2-3p in ICC cells. Furthermore, silencing Wip1 expression mimicked the suppressive effects of miR-129-2-3p upregulation on ICC cells. Interestingly, reintroduction of Wip1 expression partially abolished the miR-129-2-3p -reduced cell proliferation and invasion in ICC. Moreover, ectopic miR-129-2-3p expression hindered the ICC tumor growth in vivo. To the best of our knowledge, it is the first time to reveal that miR-129-2-3p plays a crucial role in tumor suppression in ICC pathogenesis through directly targeting Wip1. These results will aid in elucidating the roles of miR-129-2-3p in ICC, and suggest that this miRNA may provide a potential target for the treatment of ICC

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LncRNA MALAT1 Promotes Cancer Metastasis in Osteosarcoma via Activation of the PI3K-Akt Signaling Pathway

Cited by 98 publications

References 22 publications

Biology and pathogenesis of human osteosarcoma (Review)

Biology and pathogenesis of human osteosarcoma (Review)

Long non-coding RNA MALAT1 regulated ATAD2 to facilitate retinoblastoma progression by sponging miR-655-3p

MicroRNA-129-2-3p directly targets Wip1 to suppress the proliferation and invasion of intrahepatic cholangiocarcinoma

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