miR‑944 inhibits lung adenocarcinoma tumorigenesis by targeting STAT1 interaction

An,Jing  Chun; Shi,Han‑Bing; Hao,Wen‑Bo; Zhu,Kun; Ma,Bo

doi:10.3892/ol.2019.10045

miR‑944 inhibits lung adenocarcinoma tumorigenesis by targeting STAT1 interaction

Authors:
- Jing Chun An
- Han‑Bing Shi
- Wen‑Bo Hao
- Kun Zhu
- Bo Ma
View Affiliations

Affiliations: Department of Respiratory Medicine, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161000, P.R. China, Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161000, P.R. China
Published online on: February 18, 2019 https://doi.org/10.3892/ol.2019.10045
Pages: 3790-3798
Copyright: © An et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Lung adenocarcinoma (LAC) is a leading cause of cancer‑associated mortalities, particularly in developed countries. The aberrant expression of microRNAs (miRNAs) has been proven to regulate numerous diseases in the past two decades. miRNAs have been identified in almost all human cancer types. In the present study, the role of miR‑944 in LAC proliferation was examined. It was identified that miR‑944 was downregulated in LAC tissues and cells, and miR‑944 overexpression inhibited A549 and H1299 cell proliferation, as determined by the Cell Counting Kit‑8 and colony formation assay. Signal transducer and activator of transcription 1 (STAT1) was upregulated in LAC tissues and cells. Kaplan‑Meier analysis demonstrated that the 5‑year overall survival in patients with high STAT1 levels was significantly reduced, compared with patients with negative and low STAT1 expression. STAT1 was the direct target of miR‑944. Additionally, a miR‑944 mimic inhibited A549 cell growth in vitro. Collectively, these data demonstrate that miR‑944 serves a pivotal role in LAC tumor growth by targeting STAT1. The data obtained indicated that miR‑944 may be a novel biomarker and could result in potential therapies for LAC.

View Figures

View References

1	Huang TW, Lin KF, Lee CH, Chang H, Lee SC and Shieh YS: The role of thyroid transcription factor-1 and tumor differentiation in resected lung adenocarcinoma. Sci Rep. 7:142222017. View Article : Google Scholar : PubMed/NCBI
2	Vieira A and Ugalde Figueroa P: Anatomic bisegmentectomy for synchronous lung adenocarcinoma. J Vis Surg. 3:642017. View Article : Google Scholar : PubMed/NCBI
3	Zhang T, Chen L, Zhang S, Xu Y, Fan Y and Zhang L: Effects of high-intensity focused ultrasound on cisplatin-resistant human lung adenocarcinoma in vitro and in vivo. Acta Biochim Biophys Sin (Shanghai). 49:1092–1098. 2017. View Article : Google Scholar : PubMed/NCBI
4	Wu H, Meng S, Xu Q, Wang X, Wang J, Gong R, Song Y, Duan Y and Zhang Y: Gene expression profiling of lung adenocarcinoma in Xuanwei, China. Eur J Cancer Prev. 25:508–517. 2016. View Article : Google Scholar : PubMed/NCBI
5	Ni J, Zhou LL, Ding L, Zhao X, Cao H, Fan F, Li H, Lou R, Du Y, Dong S, et al: PPARγ agonist efatutazone and gefitinib synergistically inhibit the proliferation of EGFR-TKI-resistant lung adenocarcinoma cells via the PPARγ/PTEN/Akt pathway. Exp Cell Res. 361:246–256. 2017. View Article : Google Scholar : PubMed/NCBI
6	Bernhardt D, Adeberg S, Bozorgmehr F, Opfermann N, Hörner-Rieber J, König L, Kappes J, Thomas M, Unterberg A, Herth F, et al: Outcome and prognostic factors in single brain metastases from small-cell lung cancer. Strahlenther Onkol. 194:98–106. 2018. View Article : Google Scholar : PubMed/NCBI
7	Kim CS and Jeter MD: Radiation therapy, early stage non-small cell lung cancer. StatPearls. Treasure. (Island (FL)). 2018.
8	Li-Ming X, Zhao LJ, Simone CB II, Cheng C, Kang M, Wang X, Gong LL, Pang QS, Wang J, Yuan ZY and Wang P: Receipt of thoracic radiation therapy and radiotherapy dose are correlated with outcomes in a retrospective study of three hundred and six patients with extensive stage small-cell lung cancer. Radiother Oncol. 125:331–337. 2017. View Article : Google Scholar : PubMed/NCBI
9	Peng Y, Ren W, Wang H, Li M, Feng Z and Peng Z: Surgical treatment is an effective approach for patients with synchronous multiple primary lung cancers. J Cancer Res Ther. 13:702–706. 2017. View Article : Google Scholar : PubMed/NCBI
10	Nhat Tran, Alipourfard B, Abhyankar V, Nguyen K, Weidanz J and Gao J: Improved microRNA biomarkers for pathological stages in lung adenocarcinoma via clustering of dysregulated microRNA-target associations. Conf Proc IEEE Eng Med Biol Soc. 2017:2708–2711. 2017.PubMed/NCBI
11	Chang SM and Hu WW: Long non-coding RNA MALAT1 promotes oral squamous cell carcinoma development via microRNA-125b/STAT3 axis. J Cell Physiol. 233:3384–3396. 2018. View Article : Google Scholar : PubMed/NCBI
12	Bian T, Jiang D, Liu J, Yuan X, Feng J, Li Q, Zhang Q, Li X, Liu Y and Zhang J: miR-1236-3p suppresses the migration and invasion by targeting KLF8 in lung adenocarcinoma A549 cells. Biochem Biophys Res Commun. 492:461–467. 2017. View Article : Google Scholar : PubMed/NCBI
13	Sui J, Yang RS, Xu SY, Zhang YQ, Li CY, Yang S, Yin LH, Pu YP and Liang GY: Comprehensive analysis of aberrantly expressed microRNA profiles reveals potential biomarkers of human lung adenocarcinoma progression. Oncol Rep. 38:2453–2463. 2017. View Article : Google Scholar : PubMed/NCBI
14	Berrout J, Kyriakopoulou E, Moparthi L, Hogea AS, Berrout L, Ivan C, Lorger M, Boyle J, Peers C, Muench S, et al: TRPA1-FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p. Nat Commun. 8:9472017. View Article : Google Scholar : PubMed/NCBI
15	Yan W, Wu Q, Yao W, Li Y, Liu Y, Yuan J, Han R, Yang J, Ji X and Ni C: MiR-503 modulates epithelial-mesenchymal transition in silica-induced pulmonary fibrosis by targeting PI3K p85 and is sponged by lncRNA MALAT1. Sci Rep. 7:113132017. View Article : Google Scholar : PubMed/NCBI
16	Pan T, Chen W, Yuan X, Shen J, Qin C and Wang L: miR-944 inhibits metastasis of gastric cancer by preventing the epithelial-mesenchymal transition via MACC1/Met/AKT signaling. FEBS Open Bio. 7:905–914. 2017. View Article : Google Scholar : PubMed/NCBI
17	Huang J, Zheng C and Shao J, Chen L, Liu X and Shao J: Overexpression of eEF1A1 regulates G1-phase progression to promote HCC proliferation through the STAT1-cyclin D1 pathway. Biochem Biophys Res Commun. 494:542–549. 2017. View Article : Google Scholar : PubMed/NCBI
18	Hiller J, Hagl B, Effner R, Puel A, Schaller M, Mascher B, Eyerich S, Eyerich K, Jansson AF, Ring J, et al: STAT1 gain-of-function and dominant negative STAT3 mutations impair IL-17 and IL-22 immunity associated with CMC. J Invest Dermatol. 138:711–714. 2018. View Article : Google Scholar : PubMed/NCBI
19	Collins-McMillen D, Stevenson EV, Kim JH, Lee BJ, Cieply SJ, Nogalski MT, Chan GC, Frost RW III, Spohn CR and Yurochko AD: HCMV utilizes a non-traditional STAT1 activation cascade via signaling through EGFR and integrins to efficiently promote the motility, differentiation, and polarization of infected monocytes. J Virol pii. JVI.00622-17. 2017. View Article : Google Scholar
20	Liu R, Lu Z, Gu J, Liu J, Huang E, Liu X, Wang L, Yang J, Deng Y, Qian J, et al: MicroRNAs 15A and 16-1 activate signaling pathways that mediate chemotaxis of immune regulatory B cells to colorectal tumors. Gastroenterology. 154:637–651.e7. 2018. View Article : Google Scholar : PubMed/NCBI
21	Zhang X, Li X, Tan F, Yu N and Pei H: STAT1 inhibits MiR-181a expression to suppress colorectal cancer cell proliferation through PTEN/Akt. J Cell Biochem. 118:3435–3443. 2017. View Article : Google Scholar : PubMed/NCBI
22	Zhang M, Du Y, Lu R, Shu Y, Zhao W, Li Z, Zhang Y, Liu R, Yang T, Luo S, et al: Cholesterol retards senescence in bone marrow mesenchymal stem cells by modulating autophagy and ROS/p53/p21^Cip1/Waf1 pathway. Oxid Med Cell Longev. 2016:75243082016. View Article : Google Scholar : PubMed/NCBI
23	Daugherty A, Hegele RA, Mackman N, Rader DJ, Schmidt AM and Weber C: Complying with the national institutes of health guidelines and principles for rigor and reproducibility: Refutations. Arterioscler Thromb Vasc Biol. 36:1303–1304. 2016. View Article : Google Scholar : PubMed/NCBI
24	Lewis BP, Burge CB and Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 120:15–20. 2005. View Article : Google Scholar : PubMed/NCBI
25	Li M, Liang Z, He S, Zeng Y, Jing Y, Fang W, Wu K, Wang G, Ning X, Wang L, et al: Genome-wide identification of leaf abscission associated microRNAs in sugarcane (Saccharum officinarum L.). BMC Genomics. 18:7542017. View Article : Google Scholar : PubMed/NCBI
26	Zhao S, Gao X, Zang S, Li Y, Feng X and Yuan X: MicroRNA-383-5p acts as a prognostic marker and inhibitor of cell proliferation in lung adenocarcinoma by cancerous inhibitor of protein phosphatase 2A. Oncol Lett. 14:3573–3579. 2017. View Article : Google Scholar : PubMed/NCBI
27	Zhuang L, Shou T, Li K, Gao CL, Duan LC, Fang LZ, Zhang QY, Chen ZN, Zhang C, Yang ST and Li GF: MicroRNA-30e-5p promotes cell growth by targeting PTPN13 and indicates poor survival and recurrence in lung adenocarcinoma. J Cell Mol Med. 21:2852–2862. 2017. View Article : Google Scholar : PubMed/NCBI
28	Zhang Y, Chen Y, Yun H, Liu Z, Su M and Lai R: STAT1β enhances STAT1 function by protecting STAT1α from degradation in esophageal squamous cell carcinoma. Cell Death Dis. 8:e30772017. View Article : Google Scholar : PubMed/NCBI
29	Hu Y, Wang L, Gu J, Qu K and Wang Y: Identification of microRNA differentially expressed in three subtypes of non-small cell lung cancer and in silico functional analysis. Oncotarget. 8:74554–74566. 2017.PubMed/NCBI
30	Li W, Yang W, Liu Y, Chen S, Chin S, Qi X, Zhao Y, Liu H, Wang J, Mei X, et al: MicroRNA-378 enhances inhibitory effect of curcumin on glioblastoma. Oncotarget. 8:73938–73946. 2017.PubMed/NCBI
31	Zhang QL, Zhu QH, Zhang F, Xu B, Wang XQ and Chen JY: Transcriptome-wide analysis of immune-responsive microRNAs against poly (I:C) challenge in Branchiostoma belcheri by deep sequencing and bioinformatics. Oncotarget. 8:73590–73602. 2017.PubMed/NCBI
32	Yang Y, Ji C, Guo S, Su X, Zhao X, Zhang S, Liu G, Qiu X, Zhang Q, Guo H and Chen H: The miR-486-5p plays a causative role in prostate cancer through negative regulation of multiple tumor suppressor pathways. Oncotarget. 8:72835–72846. 2017.PubMed/NCBI
33	Yan S, Dang G, Zhang X, Jin C, Qin L, Wang Y, Shi M, Huang H and Duan Q: Downregulation of circulating exosomal miR-638 predicts poor prognosis in colon cancer patients. Oncotarget. 8:72220–72226. 2017. View Article : Google Scholar : PubMed/NCBI
34	Fawzy MS, Toraih EA, Ibrahiem A, Abdeldayem H, Mohamed AO and Abdel-Daim MM: Evaluation of miRNA-196a2 and apoptosis-related target genes: ANXA1, DFFA and PDCD4 expression in gastrointestinal cancer patients: A pilot study. PLoS One. 12:e01873102017. View Article : Google Scholar : PubMed/NCBI
35	Wen L, Li Y, Jiang Z, Zhang Y, Yang B and Han F: miR-944 inhibits cell migration and invasion by targeting MACC1 in colorectal cancer. Oncol Rep. 37:3415–3422. 2017. View Article : Google Scholar : PubMed/NCBI
36	He Z, Xu H, Meng Y and Kuang Y: miR-944 acts as a prognostic marker and promotes the tumor progression in endometrial cancer. Biomed Pharmacother. 88:902–910. 2017. View Article : Google Scholar : PubMed/NCBI
37	Liu Y, Zhang J, Sun X, Su Q and You C: Down-regulation of miR-29b in carcinoma associated fibroblasts promotes cell growth and metastasis of breast cancer. Oncotarget. 8:39559–39570. 2017.PubMed/NCBI
38	Borsini A, Cattaneo A, Malpighi C, Thuret S, Harrison NA; MRC ImmunoPsychiatry Consortium, ; Zunszain PA and Pariante CM: Interferon-alpha reduces human hippocampal neurogenesis and increases apoptosis via activation of distinct STAT1-dependent mechanisms. Int J Neuropsychopharmacol. 21:187–200. 2018. View Article : Google Scholar : PubMed/NCBI
39	Carbotti G, Nikpoor AR, Vacca P, Gangemi R, Giordano C, Campelli F, Ferrini S and Fabbi M: IL-27 mediates HLA class I up-regulation, which can be inhibited by the IL-6 pathway, in HLA-deficient small cell lung cancer cells. J Exp Clin Cancer Res. 36:1402017. View Article : Google Scholar : PubMed/NCBI
40	Zhang Y and Liu Z: STAT1 in cancer: Friend or foe? Discov Med. 24:19–29. 2017.PubMed/NCBI
41	Xi J, Huang Q, Wang L, Ma X, Deng Q, Kumar M, Zhou Z, Li L, Zeng Z, Young KH, et al: miR-21 depletion in macrophages promotes tumoricidal polarization and enhances PD-1 immunotherapy. Oncogene. 37:3151–3165. 2018. View Article : Google Scholar : PubMed/NCBI
42	Li J, He X, Wei W and Zhou X: MicroRNA-194 promotes osteoblast differentiation via downregulating STAT1. Biochem Biophys Res Commun. 460:482–488. 2015. View Article : Google Scholar : PubMed/NCBI
43	Li L, Li W, Chen N, Zhao H, Xu G, Zhao Y, Pan X, Zhang X, Zhou L, Yu D, et al: FLI1 exonic circular RNAs as a novel oncogenic driver to promote tumor metastasis in small cell lung cancer. Clin Cancer Res. Nov 14–2018.(Epub ahead of print).
44	Gujam FJ, McMillan DC and Edwards J: The relationship between total and phosphorylated STAT1 and STAT3 tumour cell expression, components of tumour microenvironment and survival in patients with invasive ductal breast cancer. Oncotarget. 7:77607–77621. 2016. View Article : Google Scholar : PubMed/NCBI