Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian Province, China.
Respiratory Medicine Center of Fujian Province, Quanzhou, 362000, Fujian Province, China.
BMC Pulm Med. 2022 Jul 25;22(1):285. doi: 10.1186/s12890-022-02055-2.
C1QTNF6 has been implicated as an essential component in multiple cellular and molecular preliminary event, including inflammation, glucose metabolism, endothelial cell modulation and carcinogenesis. However, the biological process and potential mechanism of C1QTNF6 in lung adenocarcinoma (LUAD) are indefinite and remain to be elucidated. Therefore, we investigated the interaction among the traits of C1QTNF6 and LUAD pathologic process.
RT-qPCR and western blot were conducted to determine the expression levels of C1QTNF6. RNA interference and overexpression of C1QTNF6 were constructed to identify the biological function of C1QTNF6 in cellular proliferative, migratory and invasive potentials in vitro. Dual-luciferase reporter assay was applied to identify the possible interaction between C1QTNF6 and miR-29a-3p. Moreover, RNA sequencing analysis of C1QTNF6 knockdown was performed to identify the potential regulatory pathways.
C1QTNF6 was upregulated in stage I LUAD tissues compared with adjacent non-cancerous tissues. Concurrently, C1QTNF6 knockdown could remarkably inhibit cell proliferation, migratory and invasive abilities, while overexpression of C1QTNF6 presented opposite results. Additionally, miR-29a-3p may serve as an upstream regulator of C1QTNF6 and reduce the expression of C1QTNF6. Subsequent experiments showed that miR-29a-3p could decrease the cell mobility and proliferation positive cell rates, as well as reduce the migratory and invasive possibilities in LUAD cells via downregulating C1QTNF6. Moreover, RNA sequencing analysis demonstrated that the cytokine-cytokine receptor interaction pathway may participate in the process of C1QTNF6 regulating tumor progression.
Our study first demonstrated that downregulation of C1QTNF6 could inhibit tumorigenesis and progression in LUAD cells negatively regulated by miR-29a-3p. These consequences could reinforce our awareness and understanding of the underlying mechanism and provide a promising therapeutic target for LUAD.
C1QTNF6 已被牵连为多种细胞和分子初步事件的重要组成部分，包括炎症、葡萄糖代谢、内皮细胞调节和致癌作用。然而，C1QTNF6 在肺腺癌（LUAD）中的生物学过程和潜在机制尚不确定，有待阐明。因此，我们研究了 C1QTNF6 与 LUAD 病理过程特征之间的相互作用。
采用 RT-qPCR 和 Western blot 检测 C1QTNF6 的表达水平。构建 C1QTNF6 的 RNA 干扰和过表达载体，以鉴定 C1QTNF6 在细胞增殖、迁移和侵袭潜能方面的生物学功能。应用双荧光素酶报告基因检测法鉴定 C1QTNF6 与 miR-29a-3p 之间的可能相互作用。此外，对 C1QTNF6 敲低的 RNA 测序分析用于鉴定潜在的调控途径。
与相邻非癌组织相比，I 期 LUAD 组织中 C1QTNF6 上调。同时，C1QTNF6 敲低可显著抑制细胞增殖、迁移和侵袭能力，而过表达 C1QTNF6 则呈现相反的结果。此外，miR-29a-3p 可能作为 C1QTNF6 的上游调节因子，降低 C1QTNF6 的表达。后续实验表明，miR-29a-3p 可通过下调 C1QTNF6 降低 LUAD 细胞的细胞迁移和增殖阳性细胞率，以及降低迁移和侵袭能力。此外，RNA 测序分析表明，细胞因子-细胞因子受体相互作用途径可能参与 C1QTNF6 调节肿瘤进展的过程。
本研究首次表明，下调 C1QTNF6 可通过 miR-29a-3p 负调控抑制 LUAD 细胞的肿瘤发生和进展。这些结果可以增强我们对潜在机制的认识和理解，并为 LUAD 提供有前途的治疗靶点。
