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Int J Biol Sci 2023; 19(9):2787-2802. doi:10.7150/ijbs.84570 This issue Cite

Research Paper

SLC5A3 is important for cervical cancer cell growth

Li Li1#, Fang-rong Shen2#✉, Qunxian Cheng1#, Jing Sun1#, Hang Li1, Hua-ting Sun2, Xia Cai1, Mengting Chen1, Baohua Yang1✉, Lifeng Wang1✉, Ling Xu1✉

1. Department of Obstetrics and Gynecology, Minhang Hospital, Fudan University, Shanghai, China.
2. Obstetrics and Gynecology Department, The First Affiliated Hospital of Soochow University, Suzhou, China.
# Equal contributors.

✉ Corresponding authors: Dr. Ling Xu (xu_lingedu.cn); Baohua Yang (baohuayangcom); Fang-rong Shen (shenfredu.cn); Lifeng Wang (wanglifengcom).

Citation:
Li L, Shen Fr, Cheng Q, Sun J, Li H, Sun Ht, Cai X, Chen M, Yang B, Wang L, Xu L. SLC5A3 is important for cervical cancer cell growth. Int J Biol Sci 2023; 19(9):2787-2802. doi:10.7150/ijbs.84570. https://www.ijbs.com/v19p2787.htm
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Abstract

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Novel molecular targets for cervical cancer must be identified. This study examined the role of SLC5A3, a myo-inositol transporter, in the pathogenesis of cervical cancer. Through boinformatics analysis, we showed that the SLC5A3 mRNA levels were upregulated in cervical cancer tissues. The upregulated SLC5A3 mRNA levels were negatively correlated with survival and progression-free interval. Genes co-expressed with SLC5A3 were enriched in multiple signaling cascades involved in cancer progression. In primary/established cervical cancer cells, SLC5A3 shRNA/knockout (KO) exerted growth-inhibitory effects and promoted cell death/apoptosis. Furthermore, SLC5A3 knockdown or KO downregulated myo-inositol levels, induced oxidative injury, and decreased Akt-mTOR activation in cervical cancer cells. In contrast, supplementation of myo-inositol or n-acetyl-L-cysteine or transduction of a constitutively active Akt1 construct mitigated SLC5A3 KO-induced cytotoxicity in cervical cancer cells. Lentiviral SLC5A3 overexpression construct transduction upregulated the cellular myo-inositol level and promoted Akt-mTOR activation, enhancing cervical cancer cell proliferation and migration. The binding of TonEBP to the SLC5A3 promoter was upregulated in cervical cancer. In vivo studies showed that intratumoral injection of SLC5A3 shRNA-expressing virus arrested cervical cancer xenograft growth in mice. SLC5A3 KO also inhibited pCCa-1 cervical cancer xenograft growth. The SLC5A3-depleted xenograft tissues exhibited myo-inositol downregulation, Akt-mTOR inactivation, and oxidative injury. Transduction of sh-TonEBP AAV construct downregulated SLC5A3 expression and inhibited pCCa-1 cervical cancer xenograft growth. Together, overexpressed SLC5A3 promotes growth of cervical cancer cells, representing as a novel therapeutic oncotarget for the devastating disease.

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APA
Li, L., Shen, F.r., Cheng, Q., Sun, J., Li, H., Sun, H.t., Cai, X., Chen, M., Yang, B., Wang, L., Xu, L. (2023). SLC5A3 is important for cervical cancer cell growth. International Journal of Biological Sciences, 19(9), 2787-2802. https://doi.org/10.7150/ijbs.84570.

ACS
Li, L.; Shen, F.r.; Cheng, Q.; Sun, J.; Li, H.; Sun, H.t.; Cai, X.; Chen, M.; Yang, B.; Wang, L.; Xu, L. SLC5A3 is important for cervical cancer cell growth. Int. J. Biol. Sci. 2023, 19 (9), 2787-2802. DOI: 10.7150/ijbs.84570.

NLM
Li L, Shen Fr, Cheng Q, Sun J, Li H, Sun Ht, Cai X, Chen M, Yang B, Wang L, Xu L. SLC5A3 is important for cervical cancer cell growth. Int J Biol Sci 2023; 19(9):2787-2802. doi:10.7150/ijbs.84570. https://www.ijbs.com/v19p2787.htm

CSE
Li L, Shen Fr, Cheng Q, Sun J, Li H, Sun Ht, Cai X, Chen M, Yang B, Wang L, Xu L. 2023. SLC5A3 is important for cervical cancer cell growth. Int J Biol Sci. 19(9):2787-2802.

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