目的：探究linc00941作为ceRNA吸附miR-203上调CC-趋化因子配体2（CC chemokine ligand 2，CCL2）的表达在食管鳞癌（esophageal squamous cell carcinoma，ESCC）中的作用机制。方法：选取南阳医学高等专科学校第一附属医院58例ESCC患者的癌组织和癌旁组织，其中，男性患者 33 例，年龄（49.3±18.6）岁，女性患者 25 例，年龄（44.6±20.7）岁。qPCR 法检测linc00941、miR-203、CCL2 在 ESCC 组织和 4 株人 ESCC 细胞系（EC9706、KYSE30、ECA109 和 TE1）以及人正常食管上皮细胞株HET-1A 细胞系中的表达。构建 linc00941-wt、linc00941-mut、CCL2-wt、CCL2-mut 质粒并分别与 miR-203 NC 或 miR-203 模拟物共转染到 293T细胞中。双荧光素酶报告基因实验验证 linc00941、miR-203、CCL2之间的相互作用。CCK-8和 Transwell实验检测细胞的增殖与侵袭能力。乳酸含量检测评价细胞的糖酵解能力。流式细胞术检测细胞的凋亡情况。糖酵解抑制剂2-DG以及linc00941共同干预ESCC细胞，以进一步观察linc00941对ESCC细胞的调控作用。结果：在ESCC组织中和细胞系中linc00941、CCL2表达均上调，miR-203表达下调（均P<0.05）。linc00941与miR-203、miR-203与CCL2的相互作用在ECA109细胞中得到证实。下调 linc00941 能够抑制 ECA109 细胞的增殖、侵袭和糖酵解，并诱导细胞凋亡，该作用被 miR-203 抑制剂部分逆转（均P<0.05）。过表达 CCL2 可以部分逆转敲减 linc00941 对 ECA109 细胞增殖、侵袭、糖酵解和凋亡的影响（均 P<0.05）。结论：linc00941能够吸附miR-203进而上调CCL2的表达，促进ESCC细胞的增殖、侵袭和糖酵解，诱导细胞凋亡。linc00941对ESCC细胞增殖、侵袭和凋亡的影响可能是通过调控糖酵解实现的。

Objective: To explore the mechanism of linc00941 adsorbing miR-203 as ceRNA and up-regulating the expression of CC chemokine ligand 2 (CCL2) in esophageal squamous cell carcinoma (ESCC). Methods: The cancer tissues and adjacent tissues of 58 ESCC patients in the First Affiliated Hospital of Nanyang Medical College were selected, including 33 male patients aged (49.3±18.6) years and 25 female patients aged (44.6±20.7) years. The differential expression of linc00941, miR-203 and CCL2 in ESCC tissue, four human ESCC cell lines (EC9706, KYSE30, ECA109 and TE1) and human normal esophageal epithelial cell line HET-1A were detected by qRT-PCR. linc00941-wt, linc00941-mut, CCL2-wt and CCL2-mut plasmids were constructed and co transfected into 293T cells with miR-203 NC or miR-203 mimic, respectively. Dual luciferase reporter gene assay was implemented to verify the interaction between linc00941, miR-203 and CCL2. In addition, CCK-8 and Transwell experiments were used to detect the proliferation and invasion of cells. The lactic acid (LA) content was measured to evaluate the glycolysis ability of the cells. The cell apoptosis was detected by flow cytometry. Glycolysis inhibitor 2-DG and linc00941 were used to intervene ESCC cells to further observe the regulatory effect of linc00941 on ESCC cells. Results: The expressions of linc00941 and CCL2 were up-regulated while the expression of miR-203 was down-regulated in ESCC tissues and cell lines (all P<0.05). The interactions of linc00941 with miR-203 and miR-203 with CCL2 were both confirmed in ECA109 cells. Knockdown of linc00941 could inhibit the proliferation, invasion, glycolysis of ECA109 cells and induce their apoptosis, which was partly reversed by miR-203 inhibitor (all P<0.05). At the same time, CCL2 overexpression could partly reverse the effects of knockdown of linc00941 on the proliferation, invasion, glycolysis and apoptosis of ECA109 cells (all P<0.05). Conclusion: linc00941 can increase the expression of CCL2 via absorbing miR-203, subsequently promote the proliferation,invasion, glycolysis of ESCC cells and induce their apoptosis. The effects of linc00941 on the proliferation, invasion and apoptosis of ESCC cells may be realized by regulating glycolysis.

广西壮族自治区卫健委重点项目（No. 2020030）