LINC00997/MicroRNA 574-3p/CUL2 Promotes Cervical Cancer Development via Mitogen-Activated Protein Kinase Signaling

ABSTRACT

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. 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 was to investigate the function and mechanism of LINC00997 in CC. Reverse transcription-quantitative PCR (RT-qPCR) revealed that LINC00997 RNA expression was also increased in CC cells and LINC00997 copy number was upregulated in CC tissues. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (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 microRNA 574-3p (miR-574-3p). Moreover, Western blot analysis was employed to detect the protein levels of mitogen-activated protein kinase (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.

KEYWORDS:

• LINC00997
• miR-574-3p
• CUL2
• MAPK signaling
• cervical cancer
• ERK/MAPK

ACKNOWLEDGMENTS

There are no acknowledgments to be made.

There are no competing interests.