LncRNA ZFPM2-AS1 drives the progression of nasopharyngeal carcinoma via modulating the downstream miR-3612/DTL signaling. Issue 6 (8th March 2022)

• Record Type: Journal Article
• Authors: Chang, Xiaojing; Jian, Lei
• Is Part Of: Anti-cancer drugs. Volume 33:Issue 6(2022)
• Page Start: 523
• Page End: 533
• Publication Date: 2022-03-08
• Subjects: apoptosis -- DTL -- miR-3612 -- nasopharyngeal carcinoma -- ZFPM2-AS1; Antineoplastic agents -- Periodicals; Cancer -- Chemotherapy -- Periodicals; Antineoplastic Agents -- therapeutic use -- Periodicals; Drug Therapy -- Periodicals; 616.994061
• DOI: 10.1097/CAD.0000000000001282
• Languages: English
• ISSNs: 0959-4973

Abstract

Abstract : LncRNA ZFPM2-AS1 has been illuminated to function as a carcinogenic driver in various human cancers. Whereas, the role of ZFPM2-AS1 in nasopharyngeal carcinoma (NPC) remains puzzled. To further understand NPC pathogenesis, we investigated the regulatory effects of ZFPM2-AS1 in NPC. Expression analysis for ZFPM2-AS1, miR-3612 and denticleless E3 ubiquitin protein ligase homolog (DTL) mRNA was carried out using real-time quantitative PCR. For the expression analysis of DTL protein, a western blot assay was applied. Cell proliferation was ascertained using the cell counting kit-8 assay and colony formation assay. Cell apoptosis was estimated based on the expression levels of BCL2-Associated X and B-cell lymphoma-2 using western blot assay. To verify the role of ZFPM2-AS1, a Xenograft model was prepared in vivo . The underlying binding between miR-3612 and ZFPM2-AS1 or DTL was validated through dual-luciferase-reporter assay or protein immunoprecipitation assay. ZFPM2-AS1 showed upregulated expression in NPC samples and cells. Meanwhile, ZFPM2-AS1 was mainly located in the cytoplasm. Knockdown of ZFPM2-AS1 restrained NPC cell proliferation and induced apoptosis, as well as suppressed tumorigenesis in animal models. ZFPM2-AS1 targeted miR-3612 whose expression was decreased in NPC samples and cells. Repression of miR-3612 aggravated NPC cell development and largely reversed the functional role of ZFPM2-AS1 silencing on NPC cell growth. MiR-3612 directly interacted with DTL, and DTL expression was upregulated in NPC. Downregulation of DTL blocked NPC cell growth, while miR-3612 inhibition partly abrogated the effects of DTL knockdown. ZFPM2-AS1 knockdown considerably restrained NPC development via targeting the miR-3612/DTL signaling. The study provided new insights to understand NPC pathogenesis.