PAX6 upstream antisense RNA (PAUPAR) inhibits colorectal cancer progression through modulation of the microRNA (miR)-17-5p / zinc finger protein 750 (ZNF750) axis

ABSTRACT

Researchers have demonstrated that long non-coding RNAs (lncRNAs) are vital in colorectal cancer (CRC) progression. Here, we aimed to explore the function of lncRNA PAX6 upstream antisense RNA (PAUPAR) in the development of CRC. In the present study, PAUPAR and microRNA (miR)-17-5p expression levels in CRC tissues and cells were examined using quantitative real-time polymerase chain reaction (qRT-PCR). Western blot analysis was adopted to examine ZNF750 expression at the protein level in CRC cells. CRC cell proliferation was examined by colony formation experiment and 5-Bromo-2-deoxyUridine (BrdU) experiment. CRC cell migration and invasion were assessed by Transwell experiments. Apoptosis was measured using the TUNEL experiment. The targeting relationship between PAUPAR and miR-17-5p was confirmed using dual-luciferase reporter gene and RNA immunoprecipitation (RIP) experiments. We demonstrated that PAUPAR was markedly down-modulated in CRC, and its low expression was significantly related to increased T stage and local lymph node metastasis. Knockdown of PAUPAR enhanced CRC cell proliferation, migration and invasion, and restrained apoptosis relative to controls, whereas PAUPAR overexpression caused the opposite effects. Moreover, rescue experiments showed that miR-17-5p inhibitor could reverse the role of PAUPAR knockdown on the malignant phenotypes of CRC cells. Additionally, PAUPAR could positively regulate the expression of ZNF750 via repressing miR-17-5p. Taken together, these findings suggest that PAUPAR/miR-17-5p/ZNF750 axis is a novel mechanism implicated in CRC progression.

Graphical abstractPAUPAR repressed the proliferation, migration and invasion of CRC cells, and promoted the apoptosis of CRC cells. PAUPAR sponged miR-17-5p and repressed its expression, and ZNF750 was demonstrated to be negatively regulated by miR-17-5p. PAUPAR could upregulate the expression of ZNF750 via downregulating miR-17-5p, and the functions of PAUPAR were dependent on its regulatory function on miR-17-5p/ZNF750 axis

KEYWORDS:

• CRC
• miR-17-5p
• PAUPAR
• ZNF750

Highlights

• PAUPAR is markedly down-modulated in CRC, and its low expression is significantly related to the unfavorable clinicopathological characteristics.

• Knockdown of PAUPAR promotes CRC cells’ proliferation, migration and invasion, and represses apoptosis.

• PAUPAR impedes CRC malignant biological features via modulating the miR-17-5p/ZNF750 axis.

Acknowledgements

We thank Hubei Yican Health Industry Co., Ltd. for its linguistic assistance during the preparation of this manuscript.

Authors contribution

Conceived and designed the experiments: Ruhui Wen, Chao Chen;

Performed the experiments: Ruhui Wen, Chao Chen, Xiaohua Zhong, Chen Hu;

Analyzed the data: Ruhui Wen, Chao Chen, Xiaohua Zhong;

Wrote the paper: Ruhui Wen, Chao Chen, Chen Hu.

All authors read and approved the final manuscript.

Data availability statement

The data used to support the findings of this study are available from the corresponding author upon request.

Disclosure statement

The authors declare that they have no competing interests.

Ethics statement

Our study was approved by the Ethics Review Board of HuiZhou Municipal Hospital.

Supplementary material

Supplemental data for this article can be accessed here.