Long noncoding RNA HOTAIR promotes the proliferation and metastasis of osteosarcoma cells through the AKT/mTOR signaling pathway

Abstract

It has been proven that long non-coding (lnc)RNAs serve an important role in the tumorigenesis and development of several types of human malignancy. Previous studies have demonstrated that the lncRNA Hox transcript antisense intergenic RNA (HOTAIR) is involved in the development various types of cancer, including osteosarcoma (OS). However, the underlying mechanisms by which it has an affect are still largely unknown. In the present study, it was observed that the expression of HOTAIR was significantly upregulated in OS tissues compared to matched adjacent normal tissues, using reverse transcription-quantitative polymerase chain reaction analysis. HOTAIR was silenced using specific small interfering RNA (siRNA/siR), siR-HOTAIR, in order to investigate its role in regulating OS cell proliferation, apoptosis, migration and invasion. siR-HOTAIR inhibited the proliferation of MG-63 cells due to the induction of G1 phase arrest. In addition, the results of in vitro assays demonstrated that the suppression of HOTAIR in MG-63 OS cells significantly reduced migration and invasion. The silencing of HOTAIR also significantly decreased the expression of matrix metalloproteinase (MMP) 2 and MMP9, but increased E-cadherin expression through regulating the RAC α serine/threonine protein kinase-mammalian target of rapamycin signaling pathway. The results indicated that siR-HOTAIR may be a potential OS therapy.

The emerging role of the long non-coding RNA HOTAIR in breast cancer development and treatment

“…Consistent to this hypothesis, findings revealed that down-regulation of HOTAIR could promote G1 cell cycle arrest [49]. So that, loss of this lin-cRNA promote expression of p27 leading to binding and prohibiting Cyclin D-CDK4 and Cyclin E-CDK2 activities [49] (Fig. 3).…”

“…Collaboration of Cyclin D1 with CDK4 and CDK6 contributes to posttranslational phosphorylation of some proteins and activity of some necessary transcription factors for transition of G1 to S cell cycle [48]. Consistent to this hypothesis, findings revealed that down-regulation of HOTAIR could promote G1 cell cycle arrest [49]. So that, loss of this lin-cRNA promote expression of p27 leading to binding and prohibiting Cyclin D-CDK4 and Cyclin E-CDK2 activities [49] (Fig.…”

“…In addition to making scaffolds and/or platforms to enable interactions of DNA with multiplex proteins, evidences demonstrate the critical effect of HOTAIR activity on cell cycle progression and proliferation by regulating different molecules. Transcription of this lincRNA could control expression of different cell cycle-dependent kinase, namely CDK2 and CDK4 as well as Cyclin E and Cyclin D1 [48,49]. Curiously, it has been shown that HOTAIR contributes to the function of Cyclin D1 through activity of STAT3.…”

STAT3-induced upregulation of long noncoding RNA HNF1A-AS1 promotes the progression of oral squamous cell carcinoma via activating Notch signaling pathway

“…It has been reported that lncRNAs can affect cell activities in human cancers by regulating the signal of some signaling pathway. For instance, lncRNA HOTAIR could activate the AKT/ mTOR signaling pathway, thereby enhancing the proliferative or migratory ability of osteosarcoma cells; 33 LncRNA MRCCAT1 improves cell metastasis in clear cell renal cell carcinoma by activating p38-MAPK signaling; 34 LncRNA HNF1A-AS1 has also been proved to be able to interact with Wnt/beta-catenin signaling pathway in both colorectal cancer 35 and osteosarcoma. 36 Notch signaling pathway is widely considered as a highly conserved cell signaling pathway.…”

LncRNA NCRNA00173 is down-regulated in pediatric osteosarcoma and suppresses cell metastasis of osteosarcoma cells through regulating PI3k/Akt pathway

“…18 Previous studies have revealed that the PI3K/Akt/mTOR pathway is particapted in the development of OS. For example, Li X et al 29 have reported that LncRNA HOTAIR could promote cell progression through Akt/mTOR pathway in OS. Furthermore, according to reports demonstrated, MDA19 could suppress the downstream protein of PI3K/Akt/mTOR pathway in OS, such as Cyclin D1, P70S6K and p-P70S6K.…”