Involvement of Dual-strand of the MiR-144 Duplex and Their Targets in the Pathogenesis of Lung Squamous Cell Carcinoma

Overview

Journal Cancer Sci

Specialty Oncology

Date 2018 Oct 31

PMID 30375717

Citations 19

Authors

Akifumi Uchida

Naohiko Seki

Keiko Mizuno

Shunsuke Misono

Yasutaka Yamada

Naoko Kikkawa

Hiroki Sanada

Tomohiro Kumamoto

Takayuki Suetsugu

Hiromasa Inoue

Affiliations

Soon will be listed here.

Abstract

The prognosis of patients with advanced-stage lung squamous cell carcinoma (LUSQ) is poor, and effective treatment protocols are limited. Our continuous analyses of antitumor microRNAs (miRNAs) and their oncogenic targets have revealed novel oncogenic pathways in LUSQ. Analyses of our original miRNA expression signatures indicated that both strands of miR-144 (miR-144-5p, the passenger strand; miR-144-3p, the guide strand) showed decreased expression in cancer tissues. Additionally, low expression of miR-144-5p significantly predicted a poor prognosis in patients with LUSQ by The Cancer Genome Atlas database analyses (overall survival, P = 0.026; disease-free survival, P = 0.023). Functional assays revealed that ectopic expression of miR-144-5p and miR-144-3p significantly blocked the malignant abilities of LUSQ cells, eg, cancer cell proliferation, migration, and invasion. In LUSQ cells, 13 and 15 genes were identified as possible oncogenic targets that might be regulated by miR-144-5p and miR-144-3p, respectively. Among these targets, we identified 3 genes (SLC44A5, MARCKS, and NCS1) that might be regulated by both strands of miR-144. Interestingly, high expression of NCS1 predicted a significantly poorer prognosis in patients with LUSQ (overall survival, P = 0.013; disease-free survival, P = 0.048). By multivariate analysis, NCS1 expression was found to be an independent prognostic factor for patients with LUSQ patients. Overexpression of NCS1 was detected in LUSQ clinical specimens, and its aberrant expression enhanced malignant transformation of LUSQ cells. Our approach, involving identification of antitumor miRNAs and their targets, will contribute to improving our understanding of the molecular pathogenesis of LUSQ.

Citing Articles

The Role of NCS1 in Immunotherapy and Prognosis of Human Cancer.

Wang G, Gan X, Zeng Y, Chen X, Kang H, Huang S Biomedicines. 2023; 11(10).

PMID: 37893139 PMC: 10604305. DOI: 10.3390/biomedicines11102765.

The Molecular Pathogenesis of Tumor-Suppressive and Target Genes: Facilitates Aggressiveness in Lung Adenocarcinoma.

Tomioka Y, Suetsugu T, Seki N, Tanigawa K, Hagihara Y, Shinmura M Cells. 2023; 12(14).

PMID: 37508549 PMC: 10378275. DOI: 10.3390/cells12141885.

MiR-101-3p targets KPNA2 to inhibit the progression of lung squamous cell carcinoma cell lines.

Dong L, Jiang H, Qiu T, Xu Y, Chen E, Huang A Histol Histopathol. 2022; 38(10):1169-1178.

PMID: 36583484 DOI: 10.14670/HH-18-573.

MiRNA expression profiling in adenocarcinoma and squamous cell lung carcinoma reveals both common and specific deregulated microRNAs.

Petkova V, Marinova D, Kyurkchiyan S, Stancheva G, Mekov E, Kachakova-Yordanova D Medicine (Baltimore). 2022; 101(33):e30027.

PMID: 35984198 PMC: 9388044. DOI: 10.1097/MD.0000000000030027.

miRNAs-mediated overexpression of Periostin is correlated with poor prognosis and immune infiltration in lung squamous cell carcinoma.

Bai X, Chen H, Oliver B Aging (Albany NY). 2022; 14(9):3757-3781.

PMID: 35508298 PMC: 9134939. DOI: 10.18632/aging.204056.

References

Wang Y, Zhang Y, Yang T, Zhao W, Wang N, Li P . Long non-coding RNA MALAT1 for promoting metastasis and proliferation by acting as a ceRNA of miR-144-3p in osteosarcoma cells. Oncotarget. 2017; 8(35):59417-59434. PMC: 5601743. DOI: 10.18632/oncotarget.19727. View

Fitzmaurice C, Allen C, Barber R, Barregard L, Bhutta Z, Brenner H . Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol. 2016; 3(4):524-548. PMC: 6103527. DOI: 10.1001/jamaoncol.2016.5688. View

Kojima S, Chiyomaru T, Kawakami K, Yoshino H, Enokida H, Nohata N . Tumour suppressors miR-1 and miR-133a target the oncogenic function of purine nucleoside phosphorylase (PNP) in prostate cancer. Br J Cancer. 2011; 106(2):405-13. PMC: 3261671. DOI: 10.1038/bjc.2011.462. View

Kabbani N, Negyessy L, Lin R, Levenson R . Interaction with neuronal calcium sensor NCS-1 mediates desensitization of the D2 dopamine receptor. J Neurosci. 2002; 22(19):8476-86. PMC: 6757796. View

Peters S, Camidge D, Shaw A, Gadgeel S, Ahn J, Kim D . Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2017; 377(9):829-838. DOI: 10.1056/NEJMoa1704795. View

Mizuno K, Seki N, Mataki H, Matsushita R, Kamikawaji K, Kumamoto T . Tumor-suppressive microRNA-29 family inhibits cancer cell migration and invasion directly targeting LOXL2 in lung squamous cell carcinoma. Int J Oncol. 2015; 48(2):450-60. PMC: 4725458. DOI: 10.3892/ijo.2015.3289. View

Uchida A, Seki N, Mizuno K, Misono S, Yamada Y, Kikkawa N . Involvement of dual-strand of the miR-144 duplex and their targets in the pathogenesis of lung squamous cell carcinoma. Cancer Sci. 2018; 110(1):420-432. PMC: 6317942. DOI: 10.1111/cas.13853. View

Bartel D . MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004; 116(2):281-97. DOI: 10.1016/s0092-8674(04)00045-5. View

Koshizuka K, Hanazawa T, Kikkawa N, Arai T, Okato A, Kurozumi A . Regulation of ITGA3 by the anti-tumor miR-199 family inhibits cancer cell migration and invasion in head and neck cancer. Cancer Sci. 2017; 108(8):1681-1692. PMC: 5543473. DOI: 10.1111/cas.13298. View

10.

Mizuno K, Mataki H, Seki N, Kumamoto T, Kamikawaji K, Inoue H . MicroRNAs in non-small cell lung cancer and idiopathic pulmonary fibrosis. J Hum Genet. 2016; 62(1):57-65. DOI: 10.1038/jhg.2016.98. View

11.

Chen C, Statt S, Chiu C, Thai P, Arif M, Adler K . Targeting myristoylated alanine-rich C kinase substrate phosphorylation site domain in lung cancer. Mechanisms and therapeutic implications. Am J Respir Crit Care Med. 2014; 190(10):1127-38. PMC: 4299640. DOI: 10.1164/rccm.201408-1505OC. View

12.

Mizuno K, Mataki H, Arai T, Okato A, Kamikawaji K, Kumamoto T . The microRNA expression signature of small cell lung cancer: tumor suppressors of miR-27a-5p and miR-34b-3p and their targeted oncogenes. J Hum Genet. 2017; 62(7):671-678. DOI: 10.1038/jhg.2017.27. View

13.

Koshizuka K, Hanazawa T, Arai T, Okato A, Kikkawa N, Seki N . Involvement of aberrantly expressed microRNAs in the pathogenesis of head and neck squamous cell carcinoma. Cancer Metastasis Rev. 2017; 36(3):525-545. DOI: 10.1007/s10555-017-9692-y. View

14.

Travis W . Pathology of lung cancer. Clin Chest Med. 2011; 32(4):669-92. DOI: 10.1016/j.ccm.2011.08.005. View

15.

Sandler A, Schiller J, Gray R, Dimery I, Brahmer J, Samant M . Retrospective evaluation of the clinical and radiographic risk factors associated with severe pulmonary hemorrhage in first-line advanced, unresectable non-small-cell lung cancer treated with Carboplatin and Paclitaxel plus bevacizumab. J Clin Oncol. 2009; 27(9):1405-12. PMC: 3527732. DOI: 10.1200/JCO.2008.16.2412. View

16.

Cao J, Han X, Qi X, Jin X, Li X . TUG1 promotes osteosarcoma tumorigenesis by upregulating EZH2 expression via miR-144-3p. Int J Oncol. 2017; 51(4):1115-1123. PMC: 5592872. DOI: 10.3892/ijo.2017.4110. View

17.

Zhou C, Wu Y, Chen G, Feng J, Liu X, Wang C . Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol. 2015; 26(9):1877-1883. DOI: 10.1093/annonc/mdv276. View

18.

Moore L, England A, Ehrlich B, Rimm D . Calcium Sensor, NCS-1, Promotes Tumor Aggressiveness and Predicts Patient Survival. Mol Cancer Res. 2017; 15(7):942-952. PMC: 5500411. DOI: 10.1158/1541-7786.MCR-16-0408. View

19.

Wu C, Xu B, Zhou Y, Ji M, Zhang D, Jiang J . Correlation between serum IL-1β and miR-144-3p as well as their prognostic values in LUAD and LUSC patients. Oncotarget. 2016; 7(52):85876-85887. PMC: 5349881. DOI: 10.18632/oncotarget.13042. View

20.

Boeckel G, Ehrlich B . NCS-1 is a regulator of calcium signaling in health and disease. Biochim Biophys Acta Mol Cell Res. 2018; 1865(11 Pt B):1660-1667. PMC: 6224314. DOI: 10.1016/j.bbamcr.2018.05.005. View