Int J Med Sci 2022; 19(13):1835-1846. doi:10.7150/ijms.76664 This issue Cite

Research Paper

Long non-coding RNA ncRuPAR regulates gastric cancer cell proliferation and apoptosis via phosphoinositide 3-kinase/protein kinase B signaling

Renjie Xu1#, Jiahui Yu2#, Shangjin Song3#, Dazhi Sun1, Lijuan Xiu1, Jinyu Xu1, Jing Zhao1, Xuan Liu1, Qing Ji4✉, Xiaoqiang Yue1✉

1. Department of Traditional Chinese Medicine, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
2. School of Traditional Chinese Medicine, Naval Medical University, Shanghai, 200433, China.
3. Strategic Support Force Xingcheng Special Duty Sanatorium, Xingcheng 125100, Liaoning Province, China.
4. Cancer Institute, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
#These authors contributed equally to this work.

Citation:
Xu R, Yu J, Song S, Sun D, Xiu L, Xu J, Zhao J, Liu X, Ji Q, Yue X. Long non-coding RNA ncRuPAR regulates gastric cancer cell proliferation and apoptosis via phosphoinositide 3-kinase/protein kinase B signaling. Int J Med Sci 2022; 19(13):1835-1846. doi:10.7150/ijms.76664. https://www.medsci.org/v19p1835.htm
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Abstract

Graphic abstract

Objective: To determine the effect and mechanism of the long non-coding RNA (lncRNA) ncRuPAR (non-protein coding RNA, upstream of coagulation factor II thrombin receptor [F2R]/protease-activated receptor-1 [PAR-1]) in human gastric cancer.

Methods: HGC-27-ncRuPAR overexpression and MGC-803-ncRuPAR-RNAi knockdown gastric cancer cell lines were established. We assessed the effect of ncRuPAR on cell proliferation, apoptosis, migration, and invasion using Cell Counting Kit 8, flow cytometry, scratch and transwell assays, respectively. Differentially expressed genes in HGC-27-ncRuPAR overexpression and HGC-27-empty vector cell lines were identified using Affymetrix GeneChip microarray analysis. Ingenuity Pathway Analysis (IPA) of the microarray results was subsequently conducted to identify ncRuPAR-enriched pathways, followed by validation using real time-quantitative PCR (RT-qPCR). As one of the top enriched pathways, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was further examined by western blotting to determine its role in ncRuPAR-mediated regulation of gastric cancer pathogenesis.

Results: ncRuPAR inhibited human gastric cancer cell proliferation and induced G1/S phase arrest and apoptosis, but did not affect migration or invasion in vitro. Overexpression of ncRuPAR in vitro was found to inhibit its known target PAR-1, as well as PI3K/Akt signaling. The downstream targets of PI3K/Akt, cyclin D1 was downregulated, but there was no change in expression level of B-cell lymphoma 2 (Bcl-2).

Conclusions: We showed that lncRNA-ncRuPAR could inhibit tumor cell proliferation and promote apoptosis of human gastric cancer cells, potentially by inhibiting PAR-1, PI3K/Akt signaling, and cyclin D1. The results suggest a potential role for lncRNAs as key regulatory hubs in GC progression.

Keywords: ncRuPAR, gastric cancer, cell proliferation, apoptosis, PI3K/Akt signaling


Citation styles

APA
Xu, R., Yu, J., Song, S., Sun, D., Xiu, L., Xu, J., Zhao, J., Liu, X., Ji, Q., Yue, X. (2022). Long non-coding RNA ncRuPAR regulates gastric cancer cell proliferation and apoptosis via phosphoinositide 3-kinase/protein kinase B signaling. International Journal of Medical Sciences, 19(13), 1835-1846. https://doi.org/10.7150/ijms.76664.

ACS
Xu, R.; Yu, J.; Song, S.; Sun, D.; Xiu, L.; Xu, J.; Zhao, J.; Liu, X.; Ji, Q.; Yue, X. Long non-coding RNA ncRuPAR regulates gastric cancer cell proliferation and apoptosis via phosphoinositide 3-kinase/protein kinase B signaling. Int. J. Med. Sci. 2022, 19 (13), 1835-1846. DOI: 10.7150/ijms.76664.

NLM
Xu R, Yu J, Song S, Sun D, Xiu L, Xu J, Zhao J, Liu X, Ji Q, Yue X. Long non-coding RNA ncRuPAR regulates gastric cancer cell proliferation and apoptosis via phosphoinositide 3-kinase/protein kinase B signaling. Int J Med Sci 2022; 19(13):1835-1846. doi:10.7150/ijms.76664. https://www.medsci.org/v19p1835.htm

CSE
Xu R, Yu J, Song S, Sun D, Xiu L, Xu J, Zhao J, Liu X, Ji Q, Yue X. 2022. Long non-coding RNA ncRuPAR regulates gastric cancer cell proliferation and apoptosis via phosphoinositide 3-kinase/protein kinase B signaling. Int J Med Sci. 19(13):1835-1846.

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