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15417786mcr190718-sup-225594_2_supp_5976867_q2skrd.pdf (1.39 MB)

Supplementary Materials from OLR1 Promotes Pancreatic Cancer Metastasis via Increased c-Myc Expression and Transcription of HMGA2

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posted on 2023-04-03, 17:01 authored by Gang Yang, Guangbing Xiong, Mengyu Feng, Fangyu Zhao, Jiangdong Qiu, Yueze Liu, Zhe Cao, Huanyu Wang, Jinshou Yang, Lei You, Lianfang Zheng, Taiping Zhang, Yupei Zhao

The supplemental figures and the sequences of primers and siRNAs. Figure S1. Verification of OLR1 expression in mice model. Figure S2. OLR1 promotes the metastasis of PC cells in intravenous mouse models. Figure S3. OLR1 increases the expression of c-Myc and HMGA2 to promote invasion and migration of PC cells. Figure S4. c-Myc promotes the transcription of HMGA2. Figure S5. OLR1 upregulates HMGA2 through c-Myc to promote PC cells metastasis. Figure S6. The relationship of OLR1, c-Myc and HMGA2 in xenograft tumors. Figure S7. High OLR1, c-Myc and HMGA2 expression is associated with poor prognosis of PC patients.

Funding

National Natural Science Foundation of China

CAMS Innovation Fund for Medical Sciences

Fundamental Research Funds for the Central Universities

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ARTICLE ABSTRACT

Pancreatic cancer is one of the most lethal human malignancies, partly because of its propensity for metastasis. However, the mechanisms of metastasis in pancreatic cancer remain unclear. Oxidized low-density lipoprotein receptor 1 (OLR1), a lectin-like scavenger receptor that recognizes several ligands, such as oxidized low-density lipoprotein, was previously reported in cardiovascular and metabolic diseases. The role and mechanism of OLR1 in pancreatic cancer is unclear. In this study, we found that OLR1 expression was significantly higher in pancreatic cancer tissues than that in adjacent normal tissues and closely associated with reduced overall survival. OLR1 promoted proliferation and metastasis of pancreatic cancer cells in vitro and in vivo. Mechanistically, OLR1 increased HMGA2 transcription by upregulating c-Myc expression to promote the metastasis of pancreatic cancer cells. In addition, patients with pancreatic cancer with high expression of OLR1–c-Myc–HMGA2 axis showed worse prognosis compared with patients with low expression of OLR1–c-Myc–HMGA2 axis. Our findings suggested that the OLR1–c-Myc–HMGA2 axis promotes metastasis of pancreatic cancer cells and may serve as potential therapeutic targets and prognosis markers for patients with pancreatic cancer.

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