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

Ruhui Wen, Chao Chen, Xiaohua Zhong, Chen Hu

Bioengineered 2021 Dec

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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.

Citation

Ruhui Wen, Chao Chen, Xiaohua Zhong, Chen Hu. PAX6 upstream antisense RNA (PAUPAR) inhibits colorectal cancer progression through modulation of the microRNA (miR)-17-5p / zinc finger protein 750 (ZNF750) axis. Bioengineered. 2021 Dec;12(1):3886-3899