MicroRNA let-7g and let-7i inhibit hepatoma cell growth concurrently via downregulation of the anti-apoptotic protein B-cell lymphoma-extra large

Wu,Lingjiao; Wang,Qiangfeng; Yao,Jian; Jiang,Han; Xiao,Cheng; Wu,Fusheng

doi:10.3892/ol.2014.2706

MicroRNA let-7g and let-7i inhibit hepatoma cell growth concurrently via downregulation of the anti-apoptotic protein B-cell lymphoma-extra large

Authors:
- Lingjiao Wu
- Qiangfeng Wang
- Jian Yao
- Han Jiang
- Cheng Xiao
- Fusheng Wu
View Affiliations

Affiliations: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China, Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
Published online on: November 12, 2014 https://doi.org/10.3892/ol.2014.2706
Pages: 213-218

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

Let‑7 family members have been identified as tumor‑suppressing microRNAs, which are important in human hepatocellular carcinoma (HCC). These family members may function differently as a result of different base sequences at the 3'end. The aim of this study was to determine the antitumor effects of miR‑let‑7g/i (let‑7g/i) on HCC cells and to investigate whether let‑7g and let‑7i have a combinatorial effect on HCC. The expression levels of let‑7g/i in hepatoma cells were determined by quantitative reverse transcription polymerase chain reaction. In addition, a 5‑ethynyl‑2'‑deoxyuridine retention assay and flow cytometry analysis were used to detect the effect of let‑7g/i on the proliferation and apoptosis of BEL‑7402 cells, respectively. The expression of anti‑apoptotic protein B‑cell lymphoma‑extra large (Bcl‑xL) was analyzed using western blot analysis. The results revealed that the expression levels of let‑7g/i were significantly decreased in HCC cell lines when compared with L‑02 cells. Furthermore, the overexpression of let‑7g/i significantly suppressed DNA replication, inhibited cell proliferation and promoted apoptosis of BEL‑7402 hepatoma cells. The expression of the anti‑apoptotic protein, Bcl‑xL, was inhibited by the combined role of let‑7g and let‑7i. We hypothesize that let‑7g and let‑7i exhibit a concurrent effect to regulate cell proliferation and the apoptosis of hepatoma cells, and this function is mediated by the Bcl‑xL protein.

View Figures

View References

1	Lujambio A and Lowe SW: The microcosmos of cancer. Nature. 482:347–355. 2012. View Article : Google Scholar : PubMed/NCBI
2	Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
3	Roush S and Slack FJ: The let-7 family of microRNAs. Trends Cell Biol. 18:505–516. 2008. View Article : Google Scholar : PubMed/NCBI
4	Esquela-Kerscher A and Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar : PubMed/NCBI
5	Gregory RI and Shiekhattar R: MicroRNA biogenesis and cancer. Cancer Res. 65:3509–3512. 2005. View Article : Google Scholar : PubMed/NCBI
6	Hou J, Lin L, Zhou W, et al: Identification of miRNomes in human liver and hepatocellular carcinoma reveals miR-199a/b-3p as therapeutic target for hepatocellular carcinoma. Cancer Cell. 19:232–243. 2011. View Article : Google Scholar : PubMed/NCBI
7	Yanaihara N, Caplen N, Bowman E, et al: Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 9:189–198. 2006. View Article : Google Scholar : PubMed/NCBI
8	Akao Y, Nakagawa Y and Naoe T: let-7 microRNA functions as a potential growth suppressor in human colon cancer cells. Biol Pharm Bull. 29:903–906. 2006. View Article : Google Scholar : PubMed/NCBI
9	Nam EJ, Yoon H, Kim SW, et al: MicroRNA expression profiles in serous ovarian carcinoma. Clin Cancer Res. 14:2690–2695. 2008. View Article : Google Scholar : PubMed/NCBI
10	Peng Y, Laser J, Shi G, et al: Antiproliferative effects by Let-7 repression of high-mobility group A2 in uterine leiomyoma. Mol Cancer Res. 6:663–673. 2008. View Article : Google Scholar : PubMed/NCBI
11	Shimizu S, Takehara T, Hikita H, et al: The let-7 family of microRNAs inhibits Bcl-xL expression and potentiates sorafenib-induced apoptosis in human hepatocellular carcinoma. J Hepatol. 52:698–704. 2010. View Article : Google Scholar : PubMed/NCBI
12	Zhu XM, Wu LJ, Xu J, Yang R and Wu FS: Let-7c microRNA expression and clinical significance in hepatocellular carcinoma. J Int Med Res. 39:2323–2329. 2011. View Article : Google Scholar
13	Hu X, Guo J, Zheng L, et al: The heterochronic microRNA let-7 inhibits cell motility by regulating the genes in the actin cytoskeleton pathway in breast cancer. Mol Cancer Res. 11:240–250. 2013. View Article : Google Scholar : PubMed/NCBI
14	Doench JG and Sharp PA: Specificity of microRNA target selection in translational repression. Genes Dev. 18:504–511. 2004. View Article : Google Scholar : PubMed/NCBI
15	Brennecke J, Stark A, Russell RB and Cohen SM: Principles of microRNA-target recognition. PLoS Biol. 3:e852005. View Article : Google Scholar : PubMed/NCBI
16	Abbott AL, Alvarez-Saavedra E, Miska EA, et al: The let-7 MicroRNA family members mir-48, mir-84, and mir-241 function together to regulate developmental timing in Caenorhabditis elegans. Dev Cell. 9:403–414. 2005. View Article : Google Scholar : PubMed/NCBI
17	Johnson CD, Esquela-Kerscher A, Stefani G, et al: The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res. 67:7713–7722. 2007. View Article : Google Scholar : PubMed/NCBI
18	Inui M, Martello G and Piccolo S: MicroRNA control of signal transduction. Nat Rev Mol Cell Biol. 11:252–263. 2010. View Article : Google Scholar : PubMed/NCBI
19	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI
20	Nicoloso MS, Spizzo R, Shimizu M, Rossi S and Calin GA: MicroRNAs-the micro steering wheel of tumour metastases. Nat Rev Cancer. 9:293–302. 2009. View Article : Google Scholar : PubMed/NCBI
21	Hunter SE, Finnegan EF, Zisoulis DG, et al: Functional genomic analysis of the let-7 regulatory network in Caenorhabditis elegans. PLoS Genet. 9:e10033532013. View Article : Google Scholar : PubMed/NCBI
22	Murray MJ, Saini HK, Siegler CA, et al: LIN28 Expression in malignant germ cell tumors downregulates let-7 and increases oncogene levels. Cancer Res. 73:4872–4884. 2013. View Article : Google Scholar : PubMed/NCBI
23	Bueno MJ, Gomez de Cedron M, Gomez-Lopez G, et al: Combinatorial effects of microRNAs to suppress the Myc oncogenic pathway. Blood. 117:6255–6266. 2011. View Article : Google Scholar : PubMed/NCBI
24	Mayr C, Hemann MT and Bartel DP: Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science. 315:1576–1579. 2007. View Article : Google Scholar : PubMed/NCBI
25	Johnson SM, Grosshans H, Shingara J, et al: RAS is regulated by the let-7 microRNA family. Cell. 120:635–647. 2005. View Article : Google Scholar : PubMed/NCBI
26	Tsang WP and Kwok TT: Let-7a microRNA suppresses therapeutics-induced cancer cell death by targeting caspase-3. Apoptosis. 13:1215–1222. 2008. View Article : Google Scholar : PubMed/NCBI
27	Watanabe J, Kushihata F, Honda K, et al: Prognostic significance of Bcl-xL in human hepatocellular carcinoma. Surgery. 135:604–612. 2004. View Article : Google Scholar : PubMed/NCBI