American Association for Cancer Research
10780432ccr160303-sup-161970_2_supp_3593636_kknkcc.png (168.35 kB)

Figure S3 from Genetic and Methylation-Induced Loss of miR-181a2/181b2 within chr9q33.3 Facilitates Tumor Growth of Cervical Cancer through the PIK3R3/Akt/FoxO Signaling Pathway

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posted on 2023-03-31, 20:20 authored by Qian Mei, Xiang Li, Kang Zhang, Zhiqiang Wu, Xiaolei Li, Yuanguang Meng, Mingzhou Guo, Guangbin Luo, Xiaobing Fu, Weidong Han

Figure S3. miR-181a2/181b2 did not exhibit significant effect on migration, invasion, and EMT of cervical cancer cells


National Natural Science Foundation of China

National Basic Science and Development Program of China

Beijing Nova Program



Purpose: Loss of Chr9q31–33 is one of the most common chromosome imbalances of cervical cancer, but the underlying mechanism has not been well documented.Experimental Design: The loss of heterozygosity (LOH) status of Chr9q31–33 was investigated utilizing 26 microsatellite markers. We detected the expression of miR-181a2/181b2 by qRT-PCR analysis of cervical cancer cell lines and 100 paired tumor samples and corresponding adjacent non-tumor tissues. Kaplan–Meier and Cox proportional hazard regression analyses were performed to identify the prognostic value of miR-181a2/181b2. Regulation of expression was analyzed by methylation-specific PCR. The tumor-suppressing effects of miR-181a2/181b2 were determined in vitro and in vivo. The target gene and signaling pathway that mediated the function of miR-181a2/181b2 were also identified.Results: Chr9q33.3 was identified as one of the most deleted regions in cervical cancer. Underexpression of miR-181a2/181b2 was detected in 46% of cervical cancer and was induced by the LOH of chr9q33.3 and promoter hypermethylation. Attenuated miR-181a2/181b2 expression predicted a poor prognostic phenotype and advanced clinical stage of cervical cancer. miR-181a2/181b2 prominently dampened cell-cycle progression, suppressed cell growth, and promoted apoptosis of tumor cells in vitro. They also effectively impeded tumor formation and growth in vivo. miR-181a2/181b2 exert the tumor suppressor ability by depressing the direct target PIK3R3 (p55γ) and consequently modulating the PIK3R3/Akt/FoxO signaling pathway.Conclusions: We demonstrated a cause-and-effect event beginning from loss of chr9q33.3, a frequent event in cervical cancer, to the underexpression of miR-181a2/181b2, leading to the elevated activation of the PI3K pathway. Clin Cancer Res; 23(2); 575–86. ©2016 AACR.