Objective: To investigate the role of long noncoding RNA MALAT1 in the occurrence and progression of cutaneous squamous cell carcinoma (CSCC).
Methods: Fifty-five tissue samples of CSCC and 10 normal epidermal tissues were collected for examination of the expression of MALAT1 using q-PCR and in situ hybridization. Human CSCC A431 cells were transfected with small interfering RNAs (siNC, siMALAT1-1, and siMALAT1-2) using Lipofectamine2000 to knock down MALAT1 gene, and the changes in the cell migration, invasion, mobility and proliferation were analyzed using Transwell assay, wound healing assay, and CCK-8 assay; the changes in the expressions of the related factors of epithelial-mesenchymal transition (EMT), including E-cadherin, vimentin, and β-catenin, were detected using qRT-PCR.
Results: Compared with normal tissues, CSCC tissues of different grades of differentiation all showed significantly increased expression of MALAT1 (P<0.001). In A431 cells, MALAT1 knockdown with siRNAs resulted in significantly lowered cell proliferation (P<0.001), migration (P<0.01), invasion (P<0.01), and mobility (P<0.01). Knocking down MALAT1 gene also caused significantly increased expressions of E-cadherin and β-catenin (P<0.01) and lowered the expression of vimentin (P<0.01) in A431 cells.
Conclusion: The long noncoding RNA MALAT1 promotes the occurrence and progression of CSCC and can potentially serve as a therapeutic target in treatment of CSCC.
目的: 探索长链非编码RNA MALAT1在皮肤鳞癌发生发展中的作用，为皮肤鳞癌的临床治疗提供基础理论依据。
方法: 收集55例皮肤鳞癌样本和10例正常皮肤组织样本，采用qRT-PCR与原位杂交方法检测MALAT1在皮肤鳞癌组织和正常组织中的表达情况。在皮肤鳞癌细胞株A431中，采用siRNAs（siNC, siMALAT1-1, siMALAT1-2）和Lipofectamine2000进行细胞转染来敲减基因，采用Transwell实验，细胞划痕实验，CCK增殖实验检测皮肤鳞癌细胞的迁移侵袭能力，运动能力和增殖能力。采用qRT-PCR方法检测A431中MALAT1与上皮间质转化（EMT）样转化相关因子（E-cadherin, Vimentin, β-catenin）的变化；明确其关系。
结果: 相比正常组织，皮肤鳞癌组织的不同分化水平上（高分化，中分化，低分化），MALAT1的表达率均升高（P < 0.001）。在皮肤鳞癌细胞A431中，转染MALAT1 siRNAs下调其表达后，与对照相比，其增殖能力（P < 0.001），迁移能力（P < 0.01），侵袭能力（P < 0.01），细胞划痕运动能力均下降（P < 0.01）。且EMT相关因子中上皮表型标志物E-cadherin，β-catenin的表达升高（P < 0.01），间质表型分子vimentin表达降低（P < 0.01）。
结论: 长链非编码RNA MALAT1在皮肤鳞癌的发生发展中起促进作用，可以为皮肤鳞癌的临床治疗提供基础理论依据。