[摘 要] 目的：探讨透明质酸介导运动受体（HMMR）在食管鳞状细胞癌（ESCC）细胞恶性进展中的作用及其潜在的分子机 制。方法：收集 2018 年 1 月至 2020 年 12 月期间在河北医科大学第四医院手术切除的 8 例 ESCC 组织及癌旁组织标本，以及 ESCC细胞KYSE-30和KYSE-150。利用WB法和免疫组化（IHC）法检测HMMR在ESCC组织中的表达情况。采用RNA干扰技 术，在KYSE-30和KYSE-150细胞中敲低HMMR表达，qPCR法和WB法检测敲低效果，通过CCK-8实验和Transwell实验分别检 测敲低HMMR对ESCC细胞增殖和侵袭能力的影响。4-硝基喹啉1-氧化物（4NQO）诱导小鼠致癌建立ESCC模型，H-E染色观察 食管的形态变化，IHC法分析HMMR、序列相似性家族83成员D（FAM83D）、上皮钙黏素（E-cadherin）和神经钙黏素（N-cadherin） 在小鼠不同癌变程度组织中的表达情况。结果：人 ESCC 组织中 HMMR 表达水平显著高于癌旁组织（均 P < 0.05）。敲低 HMMR后，KYSE-30和KYSE-150细胞的增殖和侵袭能力均显著降低（P < 0.05或P < 0.01），同时降低了FAM83D的表达水平（均 P < 0.01）。裸鼠成瘤实验中，4NQO组小鼠体质量均低于对照组（均P < 0.05）；IHC法染色结果显示，肿瘤组织中HMMR呈高表 达（P < 0.05），其中在高级别上皮内瘤变（HGIN）组织中的表达显著高于低级别上皮内瘤变（LGIN）组织（P < 0.001）。HMMR与 FAM83D、N-cadherin表达呈显著正相关（r = 0.724、0.870，均 P < 0.001），与 E-cadherin 表达呈显著负相关（r = -0.714，P < 0.001）。 结论：HMMR在ESCC组织中呈高表达，其可能通过上调FAM83D表达水平促进ESCC的进展。

[Abstract] Objective: To investigate the role of hyaluronic acid-mediated motion receptor (HMMR) in the malignant progression of esophageal squamous cell carcinoma (ESCC) cells and its potential molecular mechanisms. Methods: 8 samples of ESCC tissues and adjacent paracancerous tissues surgically removed at the Fourth Hospital of Hebei Medical University between January 2018 and December 2020, as well as ESCC cells KYSE-30 and KYSE-150, were collected. Western blotting (WB) and immunohistochemistry (IHC) were used to detect the expression of HMMR in ESCC tissues. RNA interference was used to knock down HMMR expression in KYSE-30 and KYSE-150 cells, and qPCR and WB were used to detect the knockdown effect. The effects of HMMR knockdown on the proliferation and invasion abilities of ESCC cells were detected by CCK-8 assay and Transwell assay, respectively. 4-nitroquinoline 1-oxide (4NQO) was used to induce carcinogenesis in mice and establish an ESCC model . H-E staining was used to observe the morphological changes of esophagus, and IHC was used to analyze the expressions of HMMR, FAM83D (family with sequence similarity 83 member D), E-cadherin and N-cadherin in tissues of different degrees of carcinogenesis in mice. Results: The expression level of HMMR in human ESCC tissues was significantly higher than that in adjacent paracancerous tissues (all P < 0.05). After HMMR knockdown, the proliferation and invasion abilities of KYSE-30 and KYSE-150 cells were significantly reduced (P < 0.05 or P < 0.01), and the expression level of FAM83D also decreased (all P < 0.01). In nude mouse tumor experiment, the body weight of mice in the 4NQO group was lower than that of the control group (all P < 0.05). The results of IHC staining showed that HMMR was highly expressed in tumor tissues (P < 0.05), and the expression of HMMR in high-grade intraepithelial neoplasia (HGIN) tissues was significantly higher than that in low-grade intraepithelial neoplasia (LGIN) tissues (P < 0.001). HMMR was positively correlated with the expressions of FAM83D and N-cadherin (r = 0.724, 0.870, all P < 0.001), and negatively correlated with the expression of E-cadherin (r = -0.714, P < 0.001). Conclusion: HMMR is highly expressed in ESCC tissues and may promote the progression of ESCC by up-regulating FAM83D expression.

国家自然科学基金（No. 81903118）；河北省医学科学研究课题计划资助项目（No. 20180483，No. 20240092）