Let‑7i‑5p inhibits the proliferation and metastasis of colon cancer cells by targeting kallikrein‑related peptidase 6

Song,Jingyi; Wang,Lijing; Ma,Qingxia; Yang,Yuecheng; Yang,Zhengtao; Wang,Bin; He,Ningning

doi:10.3892/or.2018.6577

Let‑7i‑5p inhibits the proliferation and metastasis of colon cancer cells by targeting kallikrein‑related peptidase 6

Authors:
- Jingyi Song
- Lijing Wang
- Qingxia Ma
- Yuecheng Yang
- Zhengtao Yang
- Bin Wang
- Ningning He
View Affiliations

Affiliations: School of Basic Medical Sciences, Qingdao University, Qingdao, Shandong 266021, P.R. China, Department of Obstetrics, Qingdao Municipal Hospital, Qingdao, Shandong 266011, P.R. China, Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao, Shandong 266021, P.R. China, School of Basic Medical Sciences, Qingdao University, Qingdao, Shandong 266021, P.R. China
Published online on: July 13, 2018 https://doi.org/10.3892/or.2018.6577
Pages: 1459-1466

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

Colorectal cancer is one of the most common types of malignancies worldwide, and as it is often diagnosed at an advanced stage, it is a serious threat to human health. MicroRNAs are important regulators of the growth and metastasis of colon cancer (CC). In the present study, the results demonstrated that kallikrein‑related peptidase 6 (KLK6) plays a critical role in suppressing colon carcinoma progression. To further investigate whether microRNAs affect the impact of KLK6, a bioinformatics approach was employed, which indicated that let‑7i‑5p may directly target KLK6. Furthermore, the expression level of let‑7i‑5p was significantly negatively correlated with the expression of KLK6 at the mRNA and protein levels in CC. Functionally, overexpression of let‑7i‑5p inhibited the proliferation and invasion of CC cells, and suppressed the growth of CC in vitro. The luciferase reporter assays revealed that let‑7i‑5p targeted the KLK6 3'‑untranslated region. Collectively, these results indicated that let‑7i‑5p inhibited the proliferation and metastasis of CC cells by targeting KLK6, thereby blocking the cell cycle and promoting apoptosis in colon cells. Therefore, the present study revealed that the let‑7i‑5p/KLK6 axis may be a potential target for new therapeutic strategies to treat colon tumors.

View Figures

View References

1	Fan NJ, Kang R, Ge XY, Li M, Liu Y, Chen HM and Gao CF: Identification alpha-2-HS-glycoprotein precursor and tubulin beta chain as serology diagnosis biomarker of colorectal cancer. Diagn Pathol. 9:532014. View Article : Google Scholar : PubMed/NCBI
2	Parkin DM, Pisani P and Ferlay J: Global cancer statistics. CA Cancer J Clin. 49:33–64, 31. 1999. View Article : Google Scholar : PubMed/NCBI
3	Kinzler KW and Vogelstein B: Lessons from hereditary colorectal cancer. Cell. 87:159–170. 1996. View Article : Google Scholar : PubMed/NCBI
4	Fearon ER and Vogelstein B: A genetic model for colorectal tumorigenesis. Cell. 61:759–767. 1990. View Article : Google Scholar : PubMed/NCBI
5	Tsuchiya K: Remodeling of cancer stem cells in gastrointestinal cancer. Nihon Rinsho. 73:855–859. 2015.PubMed/NCBI
6	Kim JT, Song EY, Chung KS, Kang MA, Kim JW, Kim SJ, Yeom YI, Kim JH, Kim KH and Lee HG: Up-regulation and clinical significance of serine protease kallikrein 6 in colon cancer. Cancer. 117:2608–2619. 2011. View Article : Google Scholar : PubMed/NCBI
7	Xie Y, Yu F, Tang W, Alade BO, Peng ZH, Wang Y, Li J and Oupický D: Synthesis and evaluation of chloroquine-containing DMAEMA copolymers as efficient anti-miRNA delivery vectors with improved endosomal escape and antimigratory activity in cancer cells. Macromol Biosci. 18:2018.doi: 10.1002/mabi.201700194. View Article : Google Scholar
8	Zeng Y, Wang KX, Xu H and Hong Y: Integrative miRNA analysis identifies hsa-miR-3154, hsa-miR-7-3, and hsa-miR-600 as potential prognostic biomarker for cervical cancer. J Cell Biochem. 119:1558–1566. 2018. View Article : Google Scholar : PubMed/NCBI
9	Barh D, Malhotra R, Ravi B and Sindhurani P: MicroRNA let-7: An emerging next-generation cancer therapeutic. Curr Oncol. 17:70–80. 2010. View Article : Google Scholar : PubMed/NCBI
10	Cohen RJ, Dennis LH and Conrad ME: Anticoagulant therapy in chronic idiopathic thrombocytopenic purpura. Blood. 31:647–652. 1968.PubMed/NCBI
11	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2^−ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
12	Sells E, Pandey R, Chen H, Skovan BA, Cui H and Ignatenko NA: Specific microRNA-mRNA regulatory network of colon cancer invasion mediated by tissue kallikrein-related peptidase 6. Neoplasia. 19:396–411. 2017. View Article : Google Scholar : PubMed/NCBI
13	Kim TW, Lee SJ, Kim JT, Kim SJ, Min JK, Bae KH, Jung H, Kim BY, Lim JS, Yang Y, et al: Kallikrein-related peptidase 6 induces chemotherapeutic resistance by attenuating auranofin-induced cell death through activation of autophagy in gastric cancer. Oncotarget. 7:85332–85348. 2016. View Article : Google Scholar : PubMed/NCBI
14	Kaback HR: The role of the phosphoenolpyruvate-phosphotransferase system in the transport of sugars by isolated membrane preparations of Escherichia coli. J Biol Chem. 243:3711–3724. 1968.PubMed/NCBI
15	Quarles RH, Shin ML and Waksman BH: A workshop on mechanisms of myelin breakdown. Ann Neurol. 19:971986. View Article : Google Scholar : PubMed/NCBI
16	Elbrønd H, Huniche B and Ostergaard L: Rabbit sphincter of Oddi and duodenum are regulated by slow waves with a common basic-mode activity. Scand J Gastroenterol. 25:534–540. 1990. View Article : Google Scholar : PubMed/NCBI
17	Nagahara H, Mimori K, Utsunomiya T, Barnard GF, Ohira M, Hirakawa K and Mori M: Clinicopathologic and biological significance of kallikrein 6 overexpression in human gastric cancer. Clin Cancer Res. 11:6800–6806. 2005. View Article : Google Scholar : PubMed/NCBI
18	Ni X, Zhang W, Huang KC, Wang Y, Ng SK, Mok SC, Berkowitz RS and Ng SW: Characterisation of human kallikrein 6/protease M expression in ovarian cancer. Br J Cancer. 91:725–731. 2004. View Article : Google Scholar : PubMed/NCBI
19	Tamir A, Jag U, Sarojini S, Schindewolf C, Tanaka T, Gharbaran R, Patel H, Sood A, Hu W, Patwa R, et al: Kallikrein family proteases KLK6 and KLK7 are potential early detection and diagnostic biomarkers for serous and papillary serous ovarian cancer subtypes. J Ovarian Res. 7:1092014. View Article : Google Scholar : PubMed/NCBI
20	Pampalakis G, Prosnikli E, Agalioti T, Vlahou A, Zoumpourlis V and Sotiropoulou G: A tumor-protective role for human kallikrein-related peptidase 6 in breast cancer mediated by inhibition of epithelial-to-mesenchymal transition. Cancer Res. 69:3779–3787. 2009. View Article : Google Scholar : PubMed/NCBI
21	Diamandis EP, Yousef GM, Soosaipillai AR and Bunting P: Human kallikrein 6 (zyme/protease M/neurosin): A new serum biomarker of ovarian carcinoma. Clin Biochem. 33:579–583. 2000. View Article : Google Scholar : PubMed/NCBI
22	Shu Z, Chen L and Ding D: miR-582-5P induces colorectal cancer cell proliferation by targeting adenomatous polyposis coli. World J Surg Oncol. 14:2392016. View Article : Google Scholar : PubMed/NCBI
23	Wang J, Li H, Wang Y, Wang L, Yan X, Zhang D, Ma X, Du Y, Liu X and Yang Y: MicroRNA-552 enhances metastatic capacity of colorectal cancer cells by targeting a disintegrin and metalloprotease 28. Oncotarget. 7:70194–70210. 2016.PubMed/NCBI
24	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
25	Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
26	de Vasconcellos JF, Byrnes C, Lee YT, Allwardt JM, Kaushal M, Rabel A and Miller JL: Tough decoy targeting of predominant let-7 miRNA species in adult human hematopoietic cells. J Transl Med. 15:1692017. View Article : Google Scholar : PubMed/NCBI