CMTM4在口腔鳞状细胞癌发生发展中的作用及机制研究

doi:10.13591/j.cnki.kqyx.2023.06.001

Abstract

Abstract:

Objective To investigate the effects of CMTM4 on oral squamous cell carcinoma(OSCC). Methods The expression of CMTM4 in OSCC was analyzed by immunohistochemistry, and the relationship between the difference of CMTM4 expression and clinicopathological parameters was analyzed by Chi-square testand Fisher's precision probability test. CMTM4 overexpression plasmid and small interference RNA plasmid were transfected into OSCC cell lines HN6 and CAL27respectively, and the effects of CMTM4 overexpression and knock-down expression on cell phenotypic behavior were observed. The changes in biological behavior of HN6 and CAL27 were analyzed by CCK8 test,plate clone formation test, wound healing assay and Transwell invasion test. Western blot was used to detect changes of related cyclins and AKT pathway proteins after the changes of CMTM4. The subcutaneous tumorigenesis experiment of nude mice further verified the effect of CMTM4 on the tumorigenesis of OSCC in vivo. Results Compared with para-carcinoma tissues, CMTM4 was highly expressed in OSCC, and the difference of CMTM4 expression was significantly correlated with age, clinical stage and pathological grade of the patients (P<0.001). In HN6 and CAL27, compared with the control group, the proliferation rate of cells became faster and the ability of migration and invasion was stronger after overexpression of CMTM4. When CMTM4 was knocked down, the cell proliferation, migration and invasion ability of HN6 and CAL27 cells decreased. Overexpression of CMTM4 increased the expression of cell cycle-related proteins CDK4, CDK6 and Cyclin D1 as well as pAKT, a protein related to AKT pathway. The expression level of these proteins decreased significantly after CMTM4's knock-down. The results of animal experiment showed that compared with the control group, the tumor volume of OSCC cells increased after CMTM4 overexpression, and decreased when CMTM4 was knocked down. Conclusion CMTM4 is highly expressed in OSCC and can promote the proliferation, invasion and migration of OSCC cell line, which may play a role by regulating cell cycle and AKT pathway.

Key words: CMTM4, oral squamous cell carcinoma, Cyclin, AKT pathway, molecular targeted therapy

CLC Number:

R739.85

HU Haiyan, GAO Teng, ZHU Zai'ou, DING Xu, WU Yunong, SONG Xiaomeng. Study on the role of CMTM4 in oral squamous cell carcinoma and its mechanism[J]. Stomatology, 2023, 43(6): 481-487.

Figures/Tables 9

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References 19

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Study on the role of CMTM4 in oral squamous cell carcinoma and its mechanism

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临床病理参数	n	CMTM4低表达	CMTM4高表达	P
年龄/岁
≥60	62	31	31	<0.001^*
<60	134	26	108
性别
男	125	40	85	0.233
女	71	17	54
部位
腭	7	2	5	0.604
舌	77	20	57
牙龈	34	10	24
颊	58	19	39
口底	14	3	11
唇	6	3	3
肿瘤大小
T1	92	22	70	0.597
T2	79	22	52
T3~4	25	8	17
淋巴结转移
N0	110	35	75	0.34
N1~3	86	22	64
临床分期
Ⅰ~Ⅱ	64	31	33	<0.001^*
Ⅲ	37	11	26
Ⅳ	95	15	80
病理分级
Ⅰ	107	43	64	<0.001^*
Ⅱ~Ⅲ	89	14	75

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