LncRNA NEAT1 Promotes the Malignant Progression of Colorectal Cancer by Targeting ZEB1 via miR-448

Abstract

Background: Long noncoding RNAs have been associated with various types of malignant tumors; however, the specific role of long noncoding RNAs in tumorigenesis still remains unclear in colorectal cancer. Here, we aim to elucidate the role of long noncoding RNA nuclear paraspeckle assembly transcript 1 in the malignant progression of colorectal cancer and investigate its underlying mechanisms. Methods: Real-time polymerase chain reaction was used to detect the expression of nuclear paraspeckle assembly transcript 1 in colorectal cancer tissues and cells. Cell Counting Kit-8 assay was used to determine the effect of nuclear paraspeckle assembly transcript 1 in proliferation. Transwell assay was used to explore the role of nuclear paraspeckle assembly transcript 1 in metastasis. Bioinformatics method was used to predict the core nuclear paraspeckle assembly transcript 1 interaction network. Real-time polymerase chain reaction was used to detect nuclear paraspeckle assembly transcript 1 and miR-448 expression levels. Western blotting was used to detect the expression levels of ZEB1. Luciferase assay was used to verify the relationship among nuclear paraspeckle assembly transcript 1, miR-448, and ZEB1. The effect of nuclear paraspeckle assembly transcript 1 on tumor growth was detected by tumorigenesis test in nude mice. Results: Long noncoding RNA–nuclear paraspeckle assembly transcript 1 was up-regulated in colorectal cancer tissues and cells. Knocking down of nuclear paraspeckle assembly transcript 1 can suppress colorectal cancer proliferation and invasion, and caused a reduction of ZEB1 expression and an increase of miR-448 expression. Furthermore, knockdown of nuclear paraspeckle assembly transcript 1 regulated miR-448/ZEB1 axis to inhibit the expression of ZEB1. miR-448 silencing can reverse the effect of nuclear paraspeckle assembly transcript 1 knockdown. Conclusion: Our result demonstrated that long noncoding RNA nuclear paraspeckle assembly transcript 1 promotes proliferation and invasion of colorectal cancer by targeting miR-448 to promote the expression of ZEB1, which may play a significant role in the tumorigenesis of colorectal cancer.

Circular RNAs in EMT-driven metastasis regulation: modulation of cancer cell plasticity, tumorigenesis and therapy resistance

“…Moreover, miR-144-3p reduces ZEB1 expression to interfere with lung cancer invasion [ 154 ]. Therefore, miRNAs and ZEB1 closely interact to regulate cancer metastasis [ 155 ].…”

The functions and mechanisms of long non-coding RNA in colorectal cancer

“…The lncRNA MNX1-AS1/PPFIA4 activates the downstream AKT/HIF-1α signaling pathway to promote COAD proliferation ( 166 ). NEAT1 can regulate the miR-448/ZEB1 axis ( 167 ), and also directly acts as a molecular sponge for miR-216b, which in turn activates YY1 to promote CRC proliferation ( 168 ). PCGEM1 is elevated in CRC tissues and cells, and it regulates CRC proliferation through the miR-129-5p/SOX4 axis and the miR-433-3p/CTCF axis ( 173 , 174 ).…”

“…Tang et al.’s study suggests that MIR497HG, as a ceRNA regulating the miR-3918/ACTG2 axis, plays a key role in CRC cell migration and invasion ( 218 ). MNX1-AS1 regulates miR-744-5p ( 165 ) or the PPFIA4/AKT/HIF-1α axis ( 166 ), playing a critical role in the invasion and migration of CRC cells.NEAT1 promotes the expression of ZEB1 by targeting miR-448 ( 167 ), or enhances the proliferation and invasion of CRC through the miR-216b/YY1 axis ( 168 ). Guan et al.…”

LncRNA PCAT6 mediates UBFD1 expression via sponging miR-545-3p in breast cancer cells

“…For examples, lncRNA HOTAIR plays a vital role in regulation of chromatin state through interacting with polycomb repressive complex 2 [ 9 ]. In breast cancer cells, elevated expression of NEAT1 (nuclear paraspeckle assembly transcript 1) increases ZEB1 expression by sponging miR-448, thereby promoting cell growth and invasion capacity [ 10 ]. Emerging evidence has shown that lncRNAs act as “miRNA-sponges” or competing endogenous RNAs (ceRNA) to decrease the miRNA-induced repression of mRNAs [ 4 ].…”