Long non-coding RNA NR2F2-AS1 regulates human osteosarcoma growth and metastasis through miR-425-5p-mediated HMGB2.

Multiple studies have revealed that long non-coding RNA (lncRNA) NR2F2-AS1 plays a role in affecting cancer cell proliferation and metastasis. Here, both in vitro and in vivo experiments were performed for investigating the function and mechanism of NR2F2-AS1 in human osteosarcoma (OS). The NR2F2-AS1 level in human OS tissues and adjacent non-tumor tissues was examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The NR2F2-AS1 overexpression model was constructed in OS cells, then cell proliferation, invasion, and apoptosis were monitored. The OS xenograft model was established in nude mice using NR2F2-AS1-overexpressed OS cells. The downstream target genes of NR2F2-AS1 were predicted. qRT-PCR and Western blot were implemented to validate the profiles of miR-425-5p and HMGB2. The targeting link between NR2F2-AS1 and miR-425-5p, miR-425-5p and HMGB2 was further probed by dual-luciferase reporter experiment. In comparison to adjacent non-tumor tissues, OS tissues showed upregulated NR2F2-AS1 expression. Higher NR2F2-AS1 level was predominantly correlated with worse clinical stages. In vivo and in vitro tests corroborated that NR2F2-AS1 overexpression spurred OS cell proliferation, growth, invasion, and choked apoptosis. Mechanistically, NR2F2-AS1 hampered miR-425-5p expression as its competitive endogenous RNA (ceRNA). Thus, NR2F2-AS1 facilitated the HMGB2 expression. However, miR-425-5p inhibited HMGB2 expression by targeting the latter. NR2F2-AS1 expedited the evolution of OS by elevating HMGB2 levels through sponging miR-425-5p. The NR2F2-AS1/miR-425-5p/HMGB2 regulatory axis is a promising target in treating human OS.

Ye J ，He H ，Chen S ，Ren Y ，Guo W ，Jin Z ... -  《-》

Circular RNA circ_UBAP2 facilitates the progression of osteosarcoma by regulating microRNA miR-637/high-mobility group box (HMGB) 2 axis.

Ma W ，Zhao X ，Gao Y ，Yao X ，Zhang J ，Xu Q ... -  《-》

Long non-coding RNA KTN1-AS1 promotes progression in pancreatic cancer through regulating microRNA-23b-3p/high-mobility group box 2 axis.

Zhang ZB ，Liu N 《Aging-US》

Long non-coding RNA XIST promotes osteosarcoma progression by targeting YAP via miR-195-5p.

The lncRNA XIST (X inactive-specific transcript) is an oncogenic lncRNA that is present in various malignant tumors; however, its role and molecular mechanisms in osteosarcoma (OS) progression remain unclear. In the current study, 40 pairs of OS tissues and matched adjacent non-tumor tissues were collected. qRT-PCR was conducted to investigate the differences in XIST expression in tissues and OS cell lines. The proliferation, invasion, and EMT status of OS cells after transfection were assessed with WST-1 assays, Transwell assays, and Western blot analysis, respectively. Whether miR-195-5p was a direct downstream target of XIST was verified by both bioinformatics target gene prediction and dual-luciferase report analysis. A mouse model was established to evaluate tumor proliferation in vivo. Our results demonstrated that XIST expression was significantly upregulated in OS tissues and cell lines and negatively correlated with clinical prognosis. XIST knockdown inhibited cancer cell proliferation and invasion in vitro, inhibited the EMT of OS cells in vitro, and suppressed subcutaneous tumor growth in vivo. Further analysis demonstrated that XIST regulated YAP expression by functioning as a competing endogenous RNA that sponged miR-195-5p in OS cells. XIST directly interacted with miR-195-5p and decreased the binding of miR-195-5p to the YAP 3'UTR, which suppressed the degradation of YAP mRNA by miR-195-5p. In conclusion, this work demonstrates that lncRNA XIST enhances OS cancer cell proliferation and invasion in part through the miR-195-5p/YAP pathway. Therefore, lncRNA XIST might be a promising therapeutic target for OS.

Yang C ，Wu K ，Wang S ，Wei G ... -  《-》

The lncRNA HOXA11-AS promotes glioma cell growth and metastasis by targeting miR-130a-5p/HMGB2.

Xu CH ，Xiao LM ，Liu Y ，Chen LK ，Zheng SY ，Zeng EM ，Li DH ... -  《-》