LncRNA IGFL2-AS1 as a ceRNA Promotes HCT116 Cell Malignant Proliferation via the miR-433-3p/PAK4 Axis.

Abstract

BACKGROUND:

Colorectal cancer is a common gastrointestinal malignancy worldwide. Many studies have proved that long noncoding RNA alterations participate in colorectal cancer development. This study sought to probe the regulatory mechanism of lncRNA IGF-like family member 2 antisense RNA 1 (IGFL2-AS1) in colorectal cancer cell malignant proliferation.

METHODS:

LncRNA IGFL2-AS1 expression in colorectal cancer cancer and para-cancerous tissues and colorectal cancer cell lines was detected via quantitative real-time polymerase chain reaction. HCT116 cells were transfected with si-IGFL2-AS1, microRNA (miR)- 433-3p inhibitor or p21 (RAC1)-activated kinase 4, PAK4 and IGFL2-AS1 overexpression vector, followed by assessment of cell proliferation and clone formation using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and colony formation assay. The subcellular localization of lncRNA IGFL2-AS1 was predicted and testified via the nuclear/cytosol fractionation assay. The downstream miRNA of lncRNA IGFL2-AS1 and downstream target of miRNA were predicted, and their binding relationships were testified using dualluciferase assay and RNA immunoprediction experiment.

RESULTS:

LncRNA IGFL2-AS1 was abundantly expressed in colorectal cancer tissues and cells. Silencing lncRNA IGFL2-AS1 discouraged HCT116 cell malignant proliferation, while lncRNA IGFL2-AS1 overexpression played an opposite role. LncRNA IGFL2-AS1 was mainly expressed in the cytoplasm of HCT116 cells. LncRNA IGFL2-AS1 bound to miR-433-3p and inhibited its expression. miR-433-3p tar geted PAK4. Silencing lncRNA IGFL2-AS1 facilitated miR-433-3p to suppress PAK4 transcription. miR-433-3p inhibition or PAK4 overexpression partly reversed the inhibition of lncRNA IGFL2-AS1 on HCT116 cell malignant proliferation.

CONCLUSION:

LncRNA IGFL2-AS1 was abundantly expressed in colorectal cancer tissues and cells, and comparatively bound to miR433-3p to facilitate PAK4 transcription, thus promoting HCT116 cell malignant proliferation.

• Authors: Shuang Liu, Xiangjie Wang, Jing Zhang, Yabin Liu, Binghui Li
• Journal: The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology (Turk J Gastroenterol) Vol. 34 Issue 5 Pg. 497-507 (05 2023) ISSN: 2148-5607 [Electronic] Turkey
• PMID: 36620931 (Publication Type: Journal Article)

Chemical References

• RNA, Antisense
• RNA, Long Noncoding
• MicroRNAs
• PAK4 protein, human
• p21-Activated Kinases
• MIRN433 microRNA, human

Topics

• Humans
• RNA, Antisense (genetics)
• RNA, Long Noncoding (genetics)
• HCT116 Cells
• Cell Line, Tumor
• Cell Movement (genetics)
• MicroRNAs (genetics, metabolism)
• Cell Proliferation (genetics)
• Colorectal Neoplasms (genetics, pathology)
• Gene Expression Regulation, Neoplastic (genetics)
• p21-Activated Kinases (genetics, metabolism)