lncRNA TINCR attenuates the proliferation and invasion, and enhances the apoptosis of cutaneous malignant melanoma cells by regulating the miR‑424‑5p/LATS1 axis

Han,Xuemei; Jia,Yuxi; Chen,Xiangru; Sun,Chengkuan; Sun,Jing

doi:10.3892/or.2021.8189

lncRNA TINCR attenuates the proliferation and invasion, and enhances the apoptosis of cutaneous malignant melanoma cells by regulating the miR‑424‑5p/LATS1 axis

Authors:
- Xuemei Han
- Yuxi Jia
- Xiangru Chen
- Chengkuan Sun
- Jing Sun
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Affiliations: Department of Neurology, The China‑Japan Union Hospital of Ji Lin University, Changchun, Jilin 130033, P.R. China, Department of Dermatology, The China‑Japan Union Hospital of Ji Lin University, Changchun, Jilin 130033, P.R. China, Department of Handsurgery, The China‑Japan Union Hospital of Ji Lin University, Changchun, Jilin 130033, P.R. China
Published online on: September 20, 2021 https://doi.org/10.3892/or.2021.8189
Article Number: 238
Copyright: © Han et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cutaneous malignant melanoma (CMM) is responsible for ≥1/2 of skin cancer‑related mortalities. The aberrant expression of long non‑coding RNAs (lncRNAs) has been associated with the development of CMM. However, to the best of our knowledge, the role of the lncRNA TINCR ubiquitin domain containing (TINCR) in CMM has not been previously investigated, and thus, the current study aimed to evaluate this in vitro and in vivo. Reverse transcription‑quantitative PCR (RT‑qPCR) was used to analyze microRNA (miR)‑424‑5p expression, and RT‑qPCR and western blotting were used to measure TINCR, large tumor suppressor kinase 1 (LATS1), cellular communication network factor 2 (CTGF), cellular communication network factor 1 (CCN1) and AXL receptor tyrosine kinase (AXL) mRNA and protein expression levels, respectively. Cell Counting Kit‑8, flow cytometry and Transwell assays were used to detect the proliferation, apoptosis and invasion of CMM cell lines, respectively. The binding sites between TINCR and miR‑424‑5p were predicted using the miRDB database. A dual luciferase reporter assay and RT‑qPCR were used to identify the relationship between TINCR and miR‑424‑5p in CMM cell lines. The bioinformatics analysis revealed that TINCR was one of the most significantly downregulated lncRNAs in CMM, and advanced stage CMM tissues showed the greatest decrease in TINCR expression. Moreover, in the collected CMM tissues and tested cell lines of the current study, TINCR expression was found to be downregulated compared with the respective controls. Notably, TINCR overexpression inhibited the expression levels of CTGF, CCN1 and AXL, decreased the proliferation and invasion, and induced the apoptosis of CMM cell lines. In addition, a mutual binding association was identified between miR‑424‑5p and TINCR in CMM cells. LATS1, a target of miR‑424‑5p, was found to be positively regulated by TINCR. TINCR activated Hippo signaling and repressed the activity of Yes 1 associated transcriptional regulator by regulating LATS1 expression, while LATS1 knockdown reversed the effect of TINCR overexpression on CMM cells. Collectively, the findings of the present study suggested that TINCR may attenuate the progression of CMM by regulating the miR‑424‑5p/LATS1 signaling axis. These results indicated that TINCR may play a tumor suppressive role in CMM.

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1	Miller AJ and Mihm MC Jr: Melanoma. N Engl J Med. 355:51–65. 2006. View Article : Google Scholar : PubMed/NCBI
2	Wu Y, Wang Y, Wang L, Yin P, Lin Y and Zhou M: Burden of melanoma in China, 1990–2017: Findings from the 2017 global burden of disease study. Int J Cancer. 147:692–701. 2020. View Article : Google Scholar : PubMed/NCBI
3	Aubuchon MM, Bolt LJ, Janssen-Heijnen ML, Verleisdonk-Bolhaar ST, van Marion A and van Berlo CL: Epidemiology, management and survival outcomes of primary cutaneous melanoma: A ten-year overview. Acta Chir Belg. 117:29–35. 2017. View Article : Google Scholar : PubMed/NCBI
4	Karlsson P, Boeryd B, Sander S, Westermark P and Rosdahl I: Increasing incidence of cutaneous malignant melanoma in children and adolescents 12–19 years of age in Sweden 1973–92. Acta Derm Venereol. 78:289–292. 2008. View Article : Google Scholar : PubMed/NCBI
5	Veierød MB, Weiderpass E, Thörn M, Hansson J, Lund E, Armstrong B and Adami HO: A prospective study of pigmentation, sun exposure, and risk of cutaneous malignant melanoma in women. J Natl Cancer Inst. 95:1530–1538. 2003. View Article : Google Scholar : PubMed/NCBI
6	Lees VC and Briggs JC: Effect of initial biopsy procedure on prognosis in Stage 1 invasive cutaneous malignant melanoma: Review of 1086 patients. Br J Surg. 78:1108–1110. 2010. View Article : Google Scholar : PubMed/NCBI
7	Tseng WW, Fadaki N and Leong SP: Metastatic tumor dormancy in cutaneous melanoma: Does surgery induce escape? Cancers (Basel). 3:730–746. 2011. View Article : Google Scholar : PubMed/NCBI
8	Kim JH, Hahn EW and Tokita N: Combination hyperthermia and radiation therapy for cutaneous malignant melanoma. Cancer. 41:2143–2148. 1978. View Article : Google Scholar : PubMed/NCBI
9	Li PF, Chen SC, Xia T, Jiang XM, Shao YF, Xiao BX and Guo JM: Non-coding RNAs and gastric cancer. World J Gastroenterol. 20:5411–5419. 2014. View Article : Google Scholar : PubMed/NCBI
10	Moran VA, Perera RJ and Khalil AM: Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs. Nucleic Acids Res. 40:6391–6400. 2012. View Article : Google Scholar : PubMed/NCBI
11	Chen X, Gao J, Yu Y, Zhao Z and Pan Y: LncRNA FOXD3-AS1 promotes proliferation, invasion and migration of cutaneous malignant melanoma via regulating miR-325/MAP3K2. Biomed Pharmacother. 120:1094382019. View Article : Google Scholar : PubMed/NCBI
12	Chen XE, Chen P, Chen S, Lu J, Ma T, Shi G and Sheng L: Long non-coding RNA FENDRR inhibits migration and invasion of cutaneous malignant melanoma cells. Biosci Rep. 40:BSR201911942020. View Article : Google Scholar : PubMed/NCBI
13	Yu S, Wang D, Shao Y, Zhang T, Xie H, Jiang X, Deng Q, Jiao Y, Yang J, Cai C and Sun L: SP1-induced lncRNA TINCR overexpression contributes to colorectal cancer progression by sponging miR-7-5p. Aging. 11:1389–1403. 2019. View Article : Google Scholar : PubMed/NCBI
14	Dong H, Hu J, Zou K, Ye M, Chen Y, Wu C, Chen X and Han M: Activation of LncRNA TINCR by H3K27 acetylation promotes Trastuzumab resistance and epithelial-mesenchymal transition by targeting MicroRNA-125b in breast cancer. Mol Cancer. 18:32019. View Article : Google Scholar : PubMed/NCBI
15	Dong L, Ding H, Li Y, Xue D and Liu Y: LncRNA TINCR is associated with clinical progression and serves as tumor suppressive role in prostate cancer. Cancer Manag Res. 10:2799–2807. 2018. View Article : Google Scholar : PubMed/NCBI
16	Smith AP, Hoek K and Becker D: Whole-genome expression profiling of the melanoma progression pathway reveals marked molecular differences between nevi/melanoma in situ and advanced-stage melanomas. Cancer Biol Ther. 9:1018–29. 2005. View Article : Google Scholar : PubMed/NCBI
17	Fagerberg L, Hallström BM, Oksvold P, Kampf C, Djureinovic D, Odeberg J, Habuka M, Tahmasebpoor S, Danielsson A, Edlund K, et al: Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics. 13:397–406. 2014. View Article : Google Scholar
18	Tang Z, Li C, Kang B, Gao G, Li C and Zhang Z: GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 45:W98–W102. 2017. View Article : Google Scholar : PubMed/NCBI
19	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PcR and the 2(-delta deltac(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
20	Mo J, Zhao X, Dong X, Liu T, Zhao N, Zhang D, Wang W, Zhang Y and Sun B: Effect of EphA2 knockdown on melanoma metastasis depends on intrinsic ephrinA1 level. Cell Oncol (Dordr). 43:655–667. 2020. View Article : Google Scholar : PubMed/NCBI
21	Babapoor S, Wu R, Kozubek J, Auidi D, Grant-Kels JM and Dadras SS: Identification of microRNAs associated with invasive and aggressive phenotype in cutaneous melanoma by next-generation sequencing. Lab Invest. 97:636–648. 2017. View Article : Google Scholar : PubMed/NCBI
22	Liu X, Fu Y, Zhang G, Zhang D, Liang N, Li F, Li C, Sui C, Jiang J, Lu H, et al: miR-424-5p promotes anoikis resistance and lung metastasis by inactivating Hippo signaling in thyroid cancer. Mol Ther Oncolytics. 15:248–260. 2019. View Article : Google Scholar : PubMed/NCBI
23	Wei S, Li Q, Li Z, Wang L, Zhang L and Xu Z: miR-424-5p promotes proliferation of gastric cancer by targeting Smad3 through TGF-β signaling pathway. Oncotarget. 7:75185–75196. 2016. View Article : Google Scholar : PubMed/NCBI
24	Sahami-Fard MH, Kheirandish S and Sheikhha MH: Expression levels of miR-143-3p and −424-5p in colorectal cancer and their clinical significance. Cancer Biomark. 24:291–297. 2019. View Article : Google Scholar : PubMed/NCBI
25	Zhang J, Liu H, Hou L, Wang G, Zhang R, Huang Y, Chen X and Zhu J: Circular RNA_LARP4 inhibits cell proliferation and invasion of gastric cancer by sponging miR-424-5p and regulating LATS1 expression. Mol Cancer. 16:1512017. View Article : Google Scholar : PubMed/NCBI
26	Furth N, Pateras IS, Rotkopf R, Vlachou V, Rivkin I, Schmitt I, Bakaev D, Gershoni A, Ainbinder E, Leshkowitz D, et al: LATS1 and LATS2 suppress breast cancer progression by maintaining cell identity and metabolic state. Life Sci Alliance. 1:e2018001712018. View Article : Google Scholar : PubMed/NCBI
27	Zhang ML, Sun WH, Wu HQ, Liu ZD and Wang P: Knockdown of microRNA-103a-3p inhibits the malignancy of thyroid cancer cells through Hippo signaling pathway by upregulating LATS1. Neoplasma. 67:1266–1278. 2020. View Article : Google Scholar : PubMed/NCBI
28	Yu T, Bachman J and Lai ZC: Mutation analysis of large tumor suppressor genes LATS1 and LATS2 supports a tumor suppressor role in human cancer. Protein Cell. 6:6–11. 2015. View Article : Google Scholar : PubMed/NCBI
29	Zhang J, Wang G, Chu SJ, Zhu JS, Zhang R, Lu WW, Xia LQ, Lu YM, Da W and Sun Q: Loss of large tumor suppressor 1 promotes growth and metastasis of gastric cancer cells through upregulation of the YAP signaling. Oncotarget. 7:16180–16193. 2016. View Article : Google Scholar : PubMed/NCBI
30	Ehmer U and Sage J: Control of proliferation and cancer growth by the hippo signaling pathway. Mol Cancer Res. 14:127–140. 2016. View Article : Google Scholar : PubMed/NCBI
31	Janse van Rensburg HJ and Yang X: The roles of the hippo pathway in cancer metastasis. Cell Signal. 28:1761–1772. 2016. View Article : Google Scholar : PubMed/NCBI
32	Yu S, Zhang M, Huang L, Ma Z, Gong X, Liu W, Zhang J, Chen L, Yu Z, Zhao W and Liu Y: ERK1 indicates good prognosis and inhibits breast cancer progression by suppressing YAP1 signaling. Aging. 11:12295–12314. 2019. View Article : Google Scholar : PubMed/NCBI
33	Brodowska K, Al-Moujahed A, Marmalidou A, Horste M, Cichy J, Miller J, Evangelos E and Vavvas D: The clinically used photosensitizer Verteporfin (VP) inhibits YAP-TEAD and human retinoblastoma cell growth in vitro without light activation. Exp Eye Res. 124:67–73. 2014. View Article : Google Scholar : PubMed/NCBI