Long non‑coding RNA HOTAIR promotes the progression of synovial sarcoma through microRNA‑126/stromal cell‑derived factor‑1 regulation

Abstract

The long non-coding RNA (lncRNA) HOTAIR is an oncogene, that has been reported to be aberrantly expressed in multiple types of malignant tumor tissues. However, its expression and association with synovial sarcoma (SS) remains unclear. The present study aimed to elucidate the expression level of HOTAIR in SS tissues and also identify its role. Reverse transcription-quantitative PCR was used to detect the expression level of HOTAIR and microRNA (miR)-126 in 54 tissue samples from patients with SS, in 10 tissue samples from synovium tissues of normal patients, and in SW982 cells. The protein expression level was measured using western blot analysis and cellular immunofluorescence. Cellular proliferation, invasion and migration were assessed using MTT, Transwell and wound healing assays, respectively. HOTAIR was expressed at high levels in SS tissues. In contrast, miR-126 was expressed at low levels in SS tissues, and was negatively correlated with HOTAIR expression. HOTAIR knockdown in SW982 cells inhibited cellular proliferation in vitro , but also significantly increased the ratio of cells in the G 1 /G 0 phase of the cell cycle, and decreased the ratio of cells in the G 2 /S phase. In addition, HOTAIR knockdown inhibited the invasion and migration of the SW982 cells, as observed in the Transwell and wound healing assays. Furthermore, HOTAIR knockdown increased miR-126 expression level and decreased the expression level of stromal cell-derived factor-1 (SDF-1) at the protein level. On the other hand, while miR-126-mimic decreased the protein expression level of SDF-1, miR-126-inhibitor increased its expression level in SW982 cells. Notably, HOTAIR knockdown or SDF-1 knockout significantly decreased the protein expression levels of CDK1, CDK2, cyclin D1, MMP-9, vimentin and N-cadherin, and significantly increased the protein expression levels of p21, p53 and E-cadherin in SW982 cells. HOTAIR was highly expressed in SS tissues, wherein it could promote the proliferation, invasion and migration of SS cells by increasing the expression of SDF-1 via miR-126 inhibition.

lncHUB2: aggregated and inferred knowledge about human and mouse lncRNAs

“…The cell line with the second highest expression of HOTAIR is PANC-1, an epithelial cell line isolated from pancreatic duct carcinoma. Consistent with this observation, HOTAIR has shown to be highly expressed in pancreatic cancer ( 75 ). The next cell line with the highest expression of HOTAIR is G401, an epithelial-like kidney cell derived from an infant rhabdoid tumor.…”

“…Across all tissues and cell types, lncHUB2 reports suggest that HOTAIR has the highest relative expression in synovial tissue and sarcoma ( Figure S6A ). There is evidence that HOTAIR promotes the progression of synovial sarcoma ( 75 ). The third highest tissue expression reported by lncHUB2 for HOTAIR is in the cervix, and HOTAIR has been associated with cervical cancer progression ( 76 ).…”

The Role of lncRNAs in Rare Tumors with a Focus on HOX Transcript Antisense RNA (HOTAIR)

“…In SS cells, HOTAIR silencing inhibited cellular proliferation, invasion and migration, promoting the G 1 /G 0 phase of the cell cycle, and inhibiting the G 2 /S phase. Finally, HOTAIR knockdown increased miR-126 expression level and decreased the expression level of stromal cell-derived factor-1 (SDF-1) [ 170 ].…”

Interaction among long non‐coding RNA, micro‐RNA and mRNA in glioma

“…The over‐expression of H19 and the down‐regulation of miR‐140 were also detected by luciferase assay, indicating that miR‐140 as a target of H19 takes part in promoting the growth of glioma cells (Ghafouri‐Fard S, et al, 2021). Vasohibin 2 (VASH2) is up‐regulated through the H19‐miR‐29a pathway (Wang F, et al, 2021) to promote angiogenesis in gliomas. Moreover, lncRNA‐ATB promotes the expression of TGR‐β2 by inhibiting miR‐200a (Yin Y, et al, 2021).…”

“…The high expression of X inactive‐specific transcript (Xist) transcribed from the X chromosome inactivation center in malignant gliomas promotes the proliferation and invasion of glioma cells, and increases the resistance of glioma cells to temozolomide. The possible mechanism is that Xist, as a ceRNA of miR‐137, binds and inhibits miR‐137, and accelerates the expression of the target gene Rac1 (Wang J, et al, 2021). H19 is a maternally imprinted gene.…”