miR-15b-5p facilitates the tumorigenicity by targeting RECK and
predicts tumour recurrence in prostate cancer
, Lu Sheng
* , Hao-Jie Zhang
, Ming Ji
, Wei-Qing Qian
Department of Urology, Huadong Hospital Afﬁliated to Fudan University, Shanghai, China
Shanghai Dingdian Biotechnology Limited Company, Shanghai, China
Received: August 3, 2017; Accepted: October 26, 2017
MicroRNAs (miRNAs) have been reported to participate in many biological behaviours of multiple malignancies. Recent studies have shown that
miR-15b-5p (miR-15b) exhibits dual roles by accelerating or blocking tumour progression. However, the molecular mechanisms by which miR-
15b contributes to prostate cancer (PCa) are still elusive. Here, miR-15b expression was found signiﬁcantly up-regulated in PCa in comparison
with the normal samples and was positively correlated with age and Gleason score in patients with PCa. Notably, PCa patients with miR-15b high
expression displayed a higher recurrence rate than those with miR-15b low expression (P = 0.0058). Knockdown of miR-15b suppressed cell
growth and invasiveness in 22RV1 and PC3 cells, while overexpression of miR-15b reversed these effects. Then, we validated that RECK acted as
a direct target of miR-15b by dual-luciferase assay and revealed the negative correlation of RECK with miR-15b expression in PCa tissues. Ectopic
expression of RECK reduced cell proliferation and invasive potential and partially abrogated the tumour-promoting effects caused by miR-15b
overexpression. Additionally, miR-15b knockdown inhibited tumour growth activity in a mouse PCa xenograft model. Taken together, our ﬁndings
indicate that miR-15b promotes the progression of PCa cells by targeting RECK and represents a potential marker for patients with PCa.
PCa is one of the most commonly diagnosed malignant tumours in
men and is responsible for the high-cancer death . Although many
treatment strategies such as surgery, hormonal therapy, radiation the-
rapy, chemotherapy and targeted therapy have been applied for
patients with PCa, most of them present with tumour metastases at
the time of diagnosis, thus resulting in poor treatment effects and low-
survival rates . Various factors have been involved in the aggressive
process of PCa, and especially those related to the key signalling
transduction or regulated by non-coding RNAs (ncRNAs) contribute to
PCa progression  Therefore, it is essential to gain insight into
understanding the molecular mechanisms of how ncRNAs modulate
PCa and identify novel therapeutic targets for the treatment of PCa.
MicroRNAs (miRNAs) are a class of small ncRNAs consisting of
about 18–25 nucleotides and regulate gene expression in many physi-
ological and pathological conditions . They can function as onco-
genes or tumour suppressors involved in multi-step tumorigenesis
, of which miR-15b exerts a dual function in different types of can-
cer. Some studies show that miR-15b expression is down-regulated
in tongue cancer , glioma , glioblastoma , ovarian cancer ,
osteosarcoma  and hepatocellular carcinoma (HCC) [11, 12], and
its low expression is associated with the poor survival [7–10] and
recurrence  of patients with cancer. In addition, the serum level
of miR-15b is decreased in non-small cell lung cancer (NSCLC) 
and HCC , indicating a potential marker for diagnosis of them.
Functionally, miR-15b inhibits cell proliferation, invasion, metastasis
and cycle progression [6, 8, 11], induces cell apoptosis [11, 15] and
reverses multidrug resistance [6, 10] by targeting multiple genes
such as Wee1, IGF1R and Rab1A [8, 10, 15], while miR-15b deletion
promotes B-cell malignancies , suggesting that miR-15b may
function as a tumour suppressor in cancer.
However, other studies reveal that miR-15b expression is up-
regulated in lung adenocarcinoma , glioma , mantle cell lym-
phoma  and uterine leiomyoma  and associates with poor
prognosis and malignant progression of patients with glioma 
and melanoma . Ectopic expression of miR-15b is linked to chro-
mosomal changes leading to cervical carcinogenesis , enhances
cell proliferation , cisplatin resistance , epithelial-mesenchy-
mal transition (EMT) and metastasis in pancreatic cancer  and
predicts the brain metastases from melanoma . These studies
indicate that miR-15b acts as an oncogene in cancer.
*Correspondence to: Lu SHENG
ª 2018 The Authors.
Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use,
distribution and reproduction in any medium, provided the original work is properly cited.
J. Cell. Mol. Med. Vol 22, No 3, 2018 pp. 1855-1863