Long Non-coding RNA KRT16P2/miR-1294/EGFR Axis Regulates Laryngeal Squamous Cell Carcinoma Cell Aggressiveness

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2020 Jul 14

PMID 32655821

Citations 8

Authors

Tao Yang

Shisheng Li

Jiajia Liu

Danhui Yin

Xinming Yang

Qinglai Tang

Shuhui Wang

Affiliations

Soon will be listed here.

Abstract

Laryngeal squamous cell carcinoma (LSCC) is one of the most commonly seen head and neck malignancies. Identifying potent markers and/or targets for early diagnosis and individualized therapies for LSCC remains a considerable challenge. The present study analyzed online data and identified lncRNA KRT16P2 as a significantly upregulated long non-coding RNA (lncRNA) in LSCC. KRT16P2 knockdown in LSCC cells inhibited cancer cell proliferation, invasion, and migration. Similar to KRT16P2, EGFR expression was also significantly upregulated in LSCC. KRT16P2 and EGFR were positively correlated in LSCC tissue samples. EGFR knockdown also dramatically inhibited LSCC cell proliferation and aggressiveness (invasion and migration). Through online data and online tools, miR-1294 was predicted to target KRT16P2 and EGFR 3'UTR simultaneously. KRT16P2 inhibited miR-1294 expression, and miR-1294 inhibited EGFR expression through direct binding. miR-1294 overexpression repressed LSCC cell proliferation and aggressiveness. The effects of KRT16P2 silence on the expression of EGFR, LSCC cell proliferation, invasion, and migration, the protein levels of ki-67, PCNA, and cleaved-Caspase 3, as well as the phosphorylation of AKT, were all significantly reversed by miR-1294 inhibition. In conclusion, we demonstrated a lncRNA KRT16P2/miR-1294/EGFR axis that regulates LSCC cell proliferation, invasion, and migration. The clinical application of this axis needs further and clinical investigation.

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References

Huang J, Zheng L, Hu Y, Wang Q . Characteristics of long non-coding RNA and its relation to hepatocellular carcinoma. Carcinogenesis. 2013; 35(3):507-14. DOI: 10.1093/carcin/bgt405. View

Zhang L, Yang F, Yuan J, Yuan S, Zhou W, Huo X . Epigenetic activation of the MiR-200 family contributes to H19-mediated metastasis suppression in hepatocellular carcinoma. Carcinogenesis. 2012; 34(3):577-86. DOI: 10.1093/carcin/bgs381. View

Pinelli V, Marchica C, Ludwig M . Allergen-induced asthma in C57Bl/6 mice: hyper-responsiveness, inflammation and remodelling. Respir Physiol Neurobiol. 2009; 169(1):36-43. DOI: 10.1016/j.resp.2009.08.005. View

Achour C, Aguilo F . Long non-coding RNA and Polycomb: an intricate partnership in cancer biology. Front Biosci (Landmark Ed). 2018; 23(11):2106-2132. DOI: 10.2741/4693. View

Almadori G, Cadoni G, Galli J, Ferrandina G, Scambia G, Exarchakos G . Epidermal growth factor receptor expression in primary laryngeal cancer: an independent prognostic factor of neck node relapse. Int J Cancer. 1999; 84(2):188-91. DOI: 10.1002/(sici)1097-0215(19990420)84:2<188::aid-ijc16>3.0.co;2-1. View

Zhang Z, Li G, Cao C, Xu Q, Wang G, Jiang X . MicroRNA-1294 targets HOXA9 and has a tumor suppressive role in osteosarcoma. Eur Rev Med Pharmacol Sci. 2018; 22(24):8582-8588. DOI: 10.26355/eurrev_201812_16621. View

Zhang Z, Wang X, Cao S, Han X, Wang Z, Zhao X . The Long Noncoding RNA TUG1 Promotes Laryngeal Cancer Proliferation and Migration. Cell Physiol Biochem. 2018; 49(6):2511-2520. DOI: 10.1159/000493876. View

Liao M, Liao W, Xu N, Li B, Liu F, Zhang S . LncRNA EPB41L4A-AS1 regulates glycolysis and glutaminolysis by mediating nucleolar translocation of HDAC2. EBioMedicine. 2019; 41:200-213. PMC: 6444057. DOI: 10.1016/j.ebiom.2019.01.035. View

Guo T, Xu H, Chen W, Wu M, Dai X . Downregulation of miR-1294 associates with prognosis and tumor progression in epithelial ovarian cancer. Eur Rev Med Pharmacol Sci. 2018; 22(22):7646-7652. DOI: 10.26355/eurrev_201811_16381. View

10.

Sun T, Ye H, Wu C, Lee G, Kantoff P . Emerging players in prostate cancer: long non-coding RNAs. Am J Clin Exp Urol. 2015; 2(4):294-9. PMC: 4297325. View

11.

Wang Z, Yan J, Zou T, Gao H . MicroRNA-1294 inhibited oral squamous cell carcinoma growth by targeting c-Myc. Oncol Lett. 2018; 16(2):2243-2250. PMC: 6036472. DOI: 10.3892/ol.2018.8967. View

12.

Wang K, Chang H . Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011; 43(6):904-14. PMC: 3199020. DOI: 10.1016/j.molcel.2011.08.018. View

13.

Moon C, Chae Y, Lee J . Targeting epidermal growth factor receptor in head and neck cancer: lessons learned from cetuximab. Exp Biol Med (Maywood). 2010; 235(8):907-20. DOI: 10.1258/ebm.2009.009181. View

14.

Liu Q, Zhang F, Wang F, Qiu J, Luo C, Zhu G . TIPE2 Inhibits Lung Cancer Growth Attributing to Promotion of Apoptosis by Regulating Some Apoptotic Molecules Expression. PLoS One. 2015; 10(5):e0126176. PMC: 4422750. DOI: 10.1371/journal.pone.0126176. View

15.

Chang L, Guo R, Yuan Z, Shi H, Zhang D . LncRNA HOTAIR Regulates CCND1 and CCND2 Expression by Sponging miR-206 in Ovarian Cancer. Cell Physiol Biochem. 2018; 49(4):1289-1303. DOI: 10.1159/000493408. View

16.

Kato H, Nakajima S, Saito Y, Takahashi S, Katoh R, Kitamura M . mTORC1 serves ER stress-triggered apoptosis via selective activation of the IRE1-JNK pathway. Cell Death Differ. 2011; 19(2):310-20. PMC: 3263505. DOI: 10.1038/cdd.2011.98. View

17.

Li D, Feng J, Wu T, Wang Y, Sun Y, Ren J . Long intergenic noncoding RNA HOTAIR is overexpressed and regulates PTEN methylation in laryngeal squamous cell carcinoma. Am J Pathol. 2012; 182(1):64-70. DOI: 10.1016/j.ajpath.2012.08.042. View

18.

Dai X, Kaushik A, Zhang J . The Emerging Role of Major Regulatory RNAs in Cancer Control. Front Oncol. 2019; 9:920. PMC: 6771296. DOI: 10.3389/fonc.2019.00920. View

19.

Li X, Zhao X, Yang B, Li Y, Liu T, Pang L . Long non-coding RNA HOXD-AS1 promotes tumor progression and predicts poor prognosis in colorectal cancer. Int J Oncol. 2018; 53(1):21-32. PMC: 5958811. DOI: 10.3892/ijo.2018.4400. View

20.

Liu K, Li L, Rusidanmu A, Wang Y, Lv X . Down-Regulation of MiR-1294 is Related to Dismal Prognosis of Patients with Esophageal Squamous Cell Carcinoma through Elevating C-MYC Expression. Cell Physiol Biochem. 2015; 36(1):100-10. DOI: 10.1159/000374056. View