MicroRNA-129-2-3p directly targets Wip1 to suppress the proliferation and invasion of intrahepatic cholangiocarcinoma

Abstract

Accumulated studies showed that numerous microRNAs (miRNAs) were aberrantly expressed in human intrahepatic cholangiocarcinoma (ICC) and contributed to the tumorigenic processes. However, whether miR-129-2-3p is implicated in the ICC initiation and progression is still limited. Here, the results revealed that miR-129-2-3p expression was notably decreased in ICC tissues and cell lines, and that a low miR-129-2-3p expression was obviously associated with distant metastasis and clinical stage. Exogenous miR-129-2-3p expression evidently repressed the proliferative and invasive abilities of ICC cells. Mechanistic studies indicated that Wild-type p53-induced phosphatase 1 (Wip1) was a direct target gene for miR-129-2-3p in ICC cells. Furthermore, silencing Wip1 expression mimicked the suppressive effects of miR-129-2-3p upregulation on ICC cells. Interestingly, reintroduction of Wip1 expression partially abolished the miR-129-2-3p -reduced cell proliferation and invasion in ICC. Moreover, ectopic miR-129-2-3p expression hindered the ICC tumor growth in vivo. To the best of our knowledge, it is the first time to reveal that miR-129-2-3p plays a crucial role in tumor suppression in ICC pathogenesis through directly targeting Wip1. These results will aid in elucidating the roles of miR-129-2-3p in ICC, and suggest that this miRNA may provide a potential target for the treatment of ICC

MicroRNA-7-5p Inhibits Migration, Invasion and Metastasis of Intrahepatic Cholangiocarcinoma by Inhibiting MyD88

“… 19 The only potentially curative treatment for ICC is radical surgery. 6 , 7 , 20 However, less than 30% of patients undergo surgical resection because the early diagnosis rate of ICC is very low. Moreover, the 5-year survival rate after ICC surgical resection is less than 45%, and the recurrence rate is about 50% from most clinical studies.…”

“…2,4 Therefore, it has important clinical significance for finding new prognostic indicators and therapeutic targets by exploring the molecular mechanism of the progression of ICC. [5][6][7] MicroRNAs (miRNAs) are highly conserved small noncoding RNAs, with lengths of approximately 17-25 nucleotides. Recently, miRNAs have been shown to be involved in multiple steps that regulate the occurrence and development of ICC.…”

“… 2 , 4 Therefore, it has important clinical significance for finding new prognostic indicators and therapeutic targets by exploring the molecular mechanism of the progression of ICC. 5 – 7 …”

Mir-129-2-3p Has Tumor Suppressor Role in Ewing Sarcoma Cell Lines and Cancer Tissue Samples

“…The expression of mir-129-2-3p was significantly decreased in EWS tumor samples, and this downregulation was more obvious in Enneking IIB patients. The tumor suppressor effect of mir-129-2-3p was shown in ovarian cancer [13], cholangiocarcinoma [14], gastric cancer [15], glial and glioneuronal tumors [16]. It was found that mir-129-3p is suppressed by DNA hypermethylation in primary gastric cancers, and its decreased expression level is associated with the clinical and pathological characteristics of individuals with gastric cancer [17].…”

The new insight of treatment in Cholangiocarcinoma

“…The Notch signaling pathway, which is highly conservative in evolution, participates in the regulation of a variety of malignant biological behaviors of tumor cells, and plays an important role in the process of CCA biogenesis. Liu et al [64] found that the expression of miR-129-2-3p in ICCA tissues and cells was reduced, and its target gene Wip1 played a tumor-suppressing effect in the progression of ICCA. The high level of Wip1 in human ICCA is associated with metastasis to lymph nodes (P=0.022).…”