Table of Contents  
Year : 2014  |  Volume : 16  |  Issue : 2  |  Page : 327-328

MicroRNA let-7a: a novel therapeutic candidate in prostate cancer

1 School of Pharmacy, Anhui Medical University; Institute for Liver Diseases of Anhui Medical University (AMU); Key Laboratory of Antiinflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, Hefei, China
2 School of Pharmacy, Anhui Medical University, Hefei, China

Date of Submission12-Sep-2013
Date of Decision07-Oct-2013
Date of Acceptance01-Dec-2013
Date of Web Publication28-Jan-2014

Correspondence Address:
Jun Li
School of Pharmacy, Anhui Medical University; Institute for Liver Diseases of Anhui Medical University (AMU); Key Laboratory of Antiinflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, Hefei
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1008-682X.123680

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How to cite this article:
Wu XQ, Huang C, Liu XH, Li J. MicroRNA let-7a: a novel therapeutic candidate in prostate cancer. Asian J Androl 2014;16:327-8

How to cite this URL:
Wu XQ, Huang C, Liu XH, Li J. MicroRNA let-7a: a novel therapeutic candidate in prostate cancer. Asian J Androl [serial online] 2014 [cited 2021 Aug 5];16:327-8. Available from: - DOI: 10.4103/1008-682X.123680

Dear Editor,

It is known that microRNA let-7a can be useful for diagnosis and therapy of cancer, including prostate cancer (PCa). [1] A recent article by Wang et al. [2] comprehensively showed that let-7a1 could inhibit the expression of insulin-like growth factor-1 receptor (IGF1R) by directly targeting the T1 and T2 sites in the 3' untranslated region (3'UTR) of IGF1R mRNA. Furthermore, they found that let-7a1-mediated IGF1R downregulation was accompanied by attenuation of Elk1 activity and c-fos expression, inhibition of PC-3 cell proliferation, cell cycle arrest and induced apoptosis and that inhibition of let-7a1 could up-regulate IGF1R accompanied by an increase of Elk1 activity and c-fos expression, thereby enhancing cell proliferation. [2] Their study is interesting and provides valuable data on the role of let-7a in PCa. Another study has [3] , in fact, demonstrated that let-7a directly bound to the 3'UTR of E2F2 (E2F family of transcription factor) and CCND2 (cyclin D2) and downregulated their expression, leading to cell-cycle arrest at the G 1 /S phase and inhibit the PC-3 cells and LNCaP cells growth, especially in hormone-refractory PCa. In addition, xenograft models of PC-3 cells confirmed the capability of let-7a to inhibit prostate tumor development in vivo. [3] Emerging evidences suggest that the let-7 family plays a crucial role in the progression of PCa by maintaining and regulating molecular features of cancer stem cells or cancer stem-like cells in PCa. [4],[5] Recently, Liu et al.[6] showed that let-7a was underexpressed in the purified CD44 + Du145, LAPC9 and LAPC4 cells. And after they infected Du145 and LAPC9 cells with pLL3.7-let-7a, both Du145 clonal development and sphere formation were inhibited. Impressively, the continuously delivered let-7a distinctly slowed tumor growth and inhibited tumor regeneration of LAPC9 cells. However, PCa cells infected with pLL3.7-let-7a keep low steady-state levels of let-7a. This phenomenon may be explained by let-7a miRNAs, which have a fast turnover rate. Another interesting finding was that let-7a caused a prominent G2/M phase arrest without inducing senescence. [6] What's more, Kong and colleagues indicated that loss of let-7 family with corresponding overexpression of enhancer of zeste homolog 2 (EZH2) contributed to human PCa aggressiveness, which could be attenuated after the formulated 3,3'-diindolylmethane (BR-DIM) invention in their ongoing phase II clinical trial in patients prior to radical prostatectomy. [7]

The above-described results demonstrate a genetic association between let-7a and PCa, supporting a potential role for let-7a in human PCa. A recent study showed that let-7a remained to significantly discriminate normal tissues from PCa patients from those of the cancer negative control group with elevated prostate-specific antigen levels (P < 0.05). [8] In any case, reduced transcription patterns of let-7a could be considered as indicators of occult tumors in the vicinity. Furthermore, Schubert et al. [9] also confirmed a significant downregulation of let-7a in the high-risk PCa cases compared to benign prostatic hyperplasia (P < 0.001). However, Pesta et al. [10] found no statistical differences in expression of let-7a in the PCa tissue samples in comparison with the BPH tissue samples. They have reminded us that the behavior of BPH did not necessarily correspond with that of normal prostatic tissue. [10]

In summary, available evidence suggests a key role for let-7a in the development of PCa although there are differences in the samples; moreover, several target genes of let-7a are associated with PCa [Table 1]. Thus, these findings indicate that let-7a may be a potential noninvasive biomarker and novel therapeutic candidate in PCa. However, the precise mechanisms of let-7a in the pathogenesis of PCa need to be elucidated. Conclusions drawn from animal model studies should be limited to animal models until they are confirmed in human PCa. Therefore, further studies are required, especially in human systems, to comprehensively explore the therapeutic potential of let-7a in PCa. The development of therapeutic agents about let-7a could result in important new innovative therapies for the treatment of PCa and other cancers.
Table 1: The role of microRNA let-7a in prostate cancer

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  Author Contributions Top

XQW conceived of the study, and drafted and revised the manuscript. CH participated in the design of the study. XHL assisted with the revising of the manuscript. JL participated in its design and coordination and revision of the manuscript. All authors read and approved the final manuscript.

  Competing Interests Top

The authors declare no competing interests.

  Acknowledgments Top

This work was supported by the National Science Foundation of China (No. 21272008, No. 81072686, No. 81273526).

  References Top

1.Barh D, Malhotra R, Ravi B, Sindhurani P. MicroRNA let-7: an emerging next-generation cancer therapeutic. Curr Oncol 2010; 17: 70-80.  Back to cited text no. 1
2.Wang LN, Chen WW, Zhang J, Li CY, Xue J, et al. The miRNA let-7a1 inhibits the expression of insulin-like growth factor 1 receptor (IGF1R) in prostate cancer PC-3 cells. Asian J Androl 2013; 15: 753-8.  Back to cited text no. 2
3.Dong Q, Meng P, Wang T, Qin W, Wang F, et al. MicroRNA let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2. PLoS ONE 2010; 5: e10147.  Back to cited text no. 3
4.Viswanathan SR, Daley GQ, Gregory RI. Selective blockade of microRNA processing by Lin28. Science 2008; 320: 97-100.  Back to cited text no. 4
5.Yang X, Lin X, Zhong X, Kaur S, Li N, et al. Double-negative feedback loop between reprogramming factor LIN28 and microRNA let-7 regulates aldehyde dehydrogenase 1-positive cancer stem cells. Cancer Res 2010; 70: 9463-72.  Back to cited text no. 5
6.Liu C, Kelnar K, Vlassov AV, Brown D, Wang J, et al. Distinct microRNA expression profiles in prostate cancer stem/progenitor cells and tumor-suppressive functions of let-7. Cancer Res 2012; 72: 3393-404.  Back to cited text no. 6
7.Kong D, Heath E, Chen W, Cher ML, Powell I, et al. Loss of let-7 up-regulates EZH2 in prostate cancer consistent with the acquisition of cancer stem cell signatures that are attenuated by BR-DIM. PLoS ONE 2012; 7: e33729.  Back to cited text no. 7
8.Hellwinkel OJ, Sellier C, Sylvester YM, Brase JC, Isbarn H, et al. A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue. Int J Mol Sci 2013; 14: 5239-49.  Back to cited text no. 8
9.Schubert M, Spahn M, Kneitz S, Scholz CJ, Joniau S, et al. Distinct microRNA expression profile in prostate cancer patients with early clinical failure and the impact of let-7 as prognostic marker in high-risk prostate cancer. PLoS ONE 2013; 14: e65064.  Back to cited text no. 9
10.Pesta M, Klecka J, Kulda V, Topolcan O, Hora M, et al. Importance of miR-20a expression in prostate cancer tissue. Anticancer Res 2010; 30: 3579-83.  Back to cited text no. 10


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