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Published on: April 25, 2018
Long non-coding RNA XIST exerts oncogenic functions in human nasopharyngeal carcinoma by targeting miR-34a-5p
Peng Song1, Lin-Feng Ye1, Cen Zhang1
1Department of Otorhinolaryngology-Head and Neck Surgery, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei, PR China.
Abstract:
Long non-coding RNA (lncRNA) X inactivate-specific transcript (XIST) has been verified as an oncogenic gene in several human malignant tumors, and its dysregulation was closed associated with tumor initiation, development and progression. Nevertheless, whether the aberrant expression of XIST in human nasopharyngeal carcinoma (NPC) is corrected with malignancy, metastasis or prognosis has not been elaborated. Here, we discovered that XIST was up-regulated in NPC tissues and higher expression of XIST contributed to a markedly poorer survival time. In addition, multivariate analysis demonstrated XIST was an independent risk factor for prognosis. XIST over-expression enhanced, while XIST silencing hampered the cell growth in NPC. Additionally, mechanistic analysis revealed that XIST up-regulated the expression of miR-34a-5p targeted gene E2F3 through acting as a competitive 'sponge' of miR-34a-5p. Taking all into account, we concluded that XIST functioned as an oncogene in NPC through up-regulating E2F3 in part through 'spongeing' miR-34a-5p.
Insights
Long non-coding RNA XIST is upregulated in nasopharyngeal carcinoma (NPC), acting as an oncogene. Higher XIST expression correlates with poor prognosis and promotes NPC cell growth by upregulating E2F3.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long non-coding RNA XIST (XIST) is implicated as an oncogene in various cancers.
- The role of XIST in nasopharyngeal carcinoma (NPC) progression and prognosis remains unclear.
Purpose of the Study:
- To investigate the expression and function of XIST in NPC.
- To elucidate the underlying molecular mechanism of XIST in NPC pathogenesis.
Main Methods:
- Quantitative real-time PCR to assess XIST expression in NPC tissues.
- Kaplan-Meier analysis for survival rates.
- Cell proliferation assays (e.g., MTT, colony formation).
- Western blotting and luciferase reporter assays to confirm molecular interactions.
Main Results:
- XIST expression was significantly upregulated in NPC tissues compared to adjacent non-cancerous tissues.
- Higher XIST expression was associated with advanced clinical stage, metastasis, and poorer patient survival.
- Multivariate analysis identified XIST as an independent prognostic factor for NPC.
- Overexpression of XIST promoted NPC cell proliferation, while its silencing inhibited growth.
- Mechanistically, XIST acts as a molecular sponge for miR-34a-5p, leading to the upregulation of its target gene E2F3.
Conclusions:
- XIST functions as an oncogene in NPC.
- XIST promotes NPC cell growth and progression by upregulating E2F3 via sponging miR-34a-5p.
- XIST may serve as a potential therapeutic target and prognostic biomarker for NPC.
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