CircMAT2B facilitates the progression of head and neck squamous cell carcinoma via sponging miR-491-5p to trigger ASCT2-mediated glutaminolysis
CircMAT2B facilitates the progression of head and neck squamous cell carcinoma via sponging miR-491-5p to trigger ASCT2-mediated glutaminolysis
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DOI：
10.1007/s11010-022-04565-3
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发表时间：
2022-10
影响因子：
4.3
通讯作者：
Jingtao Luo;Ya-fei Wang;Yun Wang;Chunli Wang;Ruoyan Liu;Ze Zhang
中科院分区：
文献类型：
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作者：
Jingtao Luo;Ya-fei Wang;Yun Wang;Chunli Wang;Ruoyan Liu;Ze Zhang
众所周知，环状RNA（circRNA）在调节病理过程（包括人类癌变）中发挥着重要作用。目前，人们对其在头颈鳞状细胞癌 (HNSCC) 中的确切作用知之甚少。在此，我们旨在研究和验证一种新型circRNA circMAT2B的作用及其在HNSCC进展中的潜在分子机制。收集了 41 对 HNSCC 肿瘤组织和 HNSCC 患者的邻近正常组织。此外，我们还表征了 HNSCC 组织和细胞系中的 circMAT2B 表达模式，并探讨了其与 HNSCC 患者预后的关系。使用 Cell Counting Kit-8、EdU 掺入、TUNEL、伤口愈合和 Transwell 测定评估细胞增殖、凋亡、迁移和侵袭的生物学功能。通过测量谷氨酰胺、谷氨酸和 α-酮戊二酸 (α-KG) 水平来评估谷氨酰胺分解。通过 RNA 免疫沉淀和荧光素酶报告基因测定验证了 circMAT2B/miR-491-5p/ASCT2 轴的调控网络。 Western blot检测ASCT2和GLS1的水平。在 HNSCC 组织和细胞系中观察到 circMAT2B 显着过表达，其高丰度与患者不良预后呈正相关。 circMAT2B 的沉默会抑制细胞增殖、迁移和侵袭以及谷氨酰胺分解。 miR-491-5p 与 ASCT2 相互作用，被确定为 circMAT2B 的下游靶标，从而参与 circMAT2B 介导的生物效应。总之，我们得出的结论是，circMAT2B可以通过竞争性内源RNA（ceRNA）的分子机制部分通过miR-491-5p/ASCT2轴调节HNSCC细胞的细胞增殖、迁移、侵袭和谷氨酰胺分解过程，这意味着HNSCC治疗的潜在circRNA靶向疗法。
Circular RNAs (circRNAs) are well-known to exert significant roles in regulating the pathological processes, including human carcinogenesis. Currently, less is known about their exact roles in head and neck squamous cell carcinoma (HNSCC). Herein, we aimed to investigate and validate the role of a novel circRNA, circMAT2B, as well as its potential molecular mechanism in HNSCC progression. A cohort of 41 paired of HNSCC tumor tissues and adjacent normal tissues from HNSCC patients were collected. Further, we characterized circMAT2B expression patterns in HNSCC tissues and cell lines, as well as exploring its association with the prognosis of HNSCC patients. Biological functions on cell proliferation, apoptosis, migration, and invasion were assessed using Cell Counting Kit-8, EdU incorporation, TUNEL, wound healing, and transwell assays. Glutaminolysis was evaluated by measuring glutamine, glutamate, and α-ketoglutarate (α-KG) levels. The regulatory network of circMAT2B/miR-491-5p/ASCT2 axis was verified by RNA immunoprecipitation and luciferase reporter assays. Western blot was conducted to detect the level of ASCT2 and GLS1. Remarkably overexpressed circMAT2B was observed in HNSCC tissues and cell lines, of which high abundance was positively correlated with patients’ poor prognosis. Silencing of circMAT2B inhibited cell proliferation, migration, and invasion, as well as glutaminolysis. miR-491-5p, interacted with ASCT2, was identified to be a downstream target of circMAT2B, thereby involving in circMAT2B-mediated biological effects. In summary, we draw a conclusion that circMAT2B could modulate the processes of cell proliferation, migration, invasion, and glutaminolysis of HNSCC cells partly via the miR-491-5p/ASCT2 axis by a molecular mechanism of competing endogenous RNA (ceRNA), implying an underlying circRNA-targeted therapy for HNSCC treatment.