Cervical cancer (CC) is a common gynecological malignancy with high morbidity and mortality. Mounting evidence has highlighted that long noncoding RNAs are essential regulators in cancer development. Herein, long intergenic non-protein coding RNA 997 (LINC00997) was identified for study due to its high expression in CC tissues. The aim of the study is to investigate the function and mechanism of LINC00997 in CC. RT-qPCR revealed that LINC00997 RNA expression was also increased in CC cells and LINC00997 copy number was upregulated in CC tissues. MTT, colony formation and Transwell assays as well as transmission electron microscopy observation exhibited that LINC00997 depletion inhibited CC cell proliferation, migration, invasion and autophagy. The relationship between LINC00997 and its downstream genes was confirmed by RNA pulldown, luciferase reporter and RNA-binding protein immunoprecipitation assays. Mechanistically, LINC00997 upregulated the expression of cullin 2 (CUL2) by interacting with miR-574-3p. Moreover, western blot analysis was employed to detect the protein levels of MAPK pathway-associated factors in CC cells. LINC00997 activated the MAPK signaling by increasing CUL2 expression, thus promoting malignant phenotypes of CC cells. In conclusion, the LINC00997/miR-574-3p/CUL2 axis contributes to CC cell proliferation, migration, invasion and autophagy via the activation of MAPK signaling.

中文翻译：

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LINC00997/miR-574-3p/CUL2通过MAPK信号促进宫颈癌发展

宫颈癌（CC）是一种常见的妇科恶性肿瘤，发病率和死亡率都很高。越来越多的证据表明，长链非编码 RNA 是癌症发展中必不可少的调节因子。在此，长基因间非蛋白质编码 RNA 997 (LINC00997) 因其在 CC 组织中的高表达而被鉴定用于研究。本研究的目的是研究 LINC00997 在 CC 中的功能和机制。RT-qPCR 显示 LINC00997 RNA 在 CC 细胞中的表达也增加，并且 LINC00997 拷贝数在 CC 组织中上调。MTT、集落形成和 Transwell 测定以及透射电子显微镜观察表明 LINC00997 消耗抑制 CC 细胞增殖、迁移、侵袭和自噬。LINC00997与其下游基因的关系通过RNA pulldown得到证实，荧光素酶报告基因和 RNA 结合蛋白免疫沉淀测定。从机制上讲，LINC00997 通过与 miR-574-3p 相互作用上调了 cullin 2 (CUL2) 的表达。此外，采用蛋白质印迹分析检测CC细胞中MAPK通路相关因子的蛋白质水平。LINC00997 通过增加 CUL2 表达激活 MAPK 信号，从而促进 CC 细胞的恶性表型。总之，LINC00997/miR-574-3p/CUL2 轴通过激活 MAPK 信号通路促进 CC 细胞增殖、迁移、侵袭和自噬。LINC00997 通过增加 CUL2 表达激活 MAPK 信号，从而促进 CC 细胞的恶性表型。总之，LINC00997/miR-574-3p/CUL2 轴通过激活 MAPK 信号通路促进 CC 细胞增殖、迁移、侵袭和自噬。LINC00997 通过增加 CUL2 表达激活 MAPK 信号，从而促进 CC 细胞的恶性表型。总之，LINC00997/miR-574-3p/CUL2 轴通过激活 MAPK 信号通路促进 CC 细胞增殖、迁移、侵袭和自噬。