MiR-21 promotes intrahepatic cholangiocarcinoma proliferation and growth <i>in vitro</i> and <i>in vivo</i> by targeting PTPN14 and PTEN

Wang, Lijuan; He, Chenchen; Sui, Xin; Cai, Mingjun; Zhou, Chen; Ma, Jinlu; Wu, Lei; Wang, Hao; Han, Suxia; Zhu, Qing

doi:10.18632/oncotarget.3465

Cited by 99 publications

(96 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CCA usually metastasize and cause relapse because it is commonly diagnosed in the advanced stage of the disease, and leads to poor prognosis [2][3][4]. Many studies have revealed that numerous genes are involved in CCA [5][6][7][8][9] and many therapeutic strategies have been developed to treat CCA [10][11][12]; however, the survival rate for CCA patients is still low [13]. In this case, the pathogenesis and progression of this malignancy remains to be investigated and new therapeutic targets need to be explored.…”

Section: Introductionmentioning

confidence: 99%

miR-191 Inhibition Induces Apoptosis Through Reactivating Secreted Frizzled-Related Protein-1 in Cholangiocarcinoma

Kang

Leng

Liu

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Cholangiocarcinoma (CCA) is one of the most common malignant tumors of the biliary tract originating from biliary epithelial cells. Although many therapeutic strategies have been developed to treat CCA, the survival rate for CCA patients is still quite low. Thus it is urgent to elucidate the pathogenesis of CCA and to explore novel therapeutic targets. miR-191 has been shown to be associated with many human solid cancers, but the function of miR-191 in CCA is still poorly understood. Methods: We first investigated the expression level of miR-191 in human CCA tissues and cell lines with quantitative real-time PCR (qRT-PCR). The effects of miR-191 on CCA cells were determined by Cell Counting Kit-8 assay, colony formation assay and acridine orange/ethidium bromide staining. Finally, we utilized qRT-PCR, western blot and luciferase reporter assays to verify the miR-191 target gene. Results: We showed that miR-191 was up-regulated in CCA cell lines and patients. Knockdown of miR-191 by transfection of its inhibitor sequence blocked RBE cells viability and induced apoptosis of RBE cells. Both qRT-PCR and western blot analysis showed that the secreted frizzled-related protein-1 (sFRP1) level was negatively correlated with that of miR-191. Luciferase assay validated that sFRP1 was a direct target of miR-191. Moreover, knockdown of miR-191 led to suppression of Wnt/β-catenin signaling activation. Co-transfection of sFRP1 small interfering RNA (siRNA) and miR-191 inhibitor re-activated the Wnt/β-catenin signaling pathway as detected by an increased level of β-catenin and phosphorylation of GSK-3β, and restored the expression of survivin and c-myc in RBE cells. Co-transfection of sFRP1 siRNA with miR-191 inhibitor restored the colony formation ability and viability of RBE cells. Conclusion: Taken together, our results demonstrate a novel insight into miR-191 biological function in CCA. Our findings suggest that miR-191 is a potential therapeutic target of CCA treatment.

show abstract

Section: Introductionmentioning

confidence: 99%

miR-191 Inhibition Induces Apoptosis Through Reactivating Secreted Frizzled-Related Protein-1 in Cholangiocarcinoma

Kang

Leng

Liu

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…PTEN is a well-known tumor suppressor gene that is often mutated in cancer and was already functionally connected to development of GBC [58, 100, 101]. Wang et al identified PTEN as a direct target of miRNA-21 in BTC [84]. To determine the clinical significance of this result, they performed Kaplan-Meier analyses and could demonstrate that high miRNA-21 correlated with poor disease-free and overall survival, whereas high PTEN expression correlated with enhanced disease-free and overall survival.…”

Section: Microrna and Btcmentioning

confidence: 99%

“…PDCD4 is a tumor suppressor gene that regulates various aspects of carcinogenesis in different types of cancer and whose downregulation or loss is associated with poor prognosis [106–108]. Another direct target of miRNA-21 in BTC is PTPN14 [84], which was shown to be a negative regulator of metastasis as well as of the potentially cancer-driving Hippo/YAP pathway [109, 110]. …”

Section: Microrna and Btcmentioning

confidence: 99%

“…A similar result was seen for discrimination between patients with BTC and BBD, where miRNA-21 showed approximately twice the sensitivity of CA19-9 (71.2% versus 36.1%), but, again, combination of both factors resulted in overall better sensitivity (79.8%) [93]. Further evidence that qualifies secreted miRNA-21 as a potential biomarker comes from a study conducted by Wang et al, in which they measured serum levels of miRNA-21 in patients with IHC compared to healthy individuals [84]. Serum miRNA-21 was significantly enhanced in IHC samples and, in line with the study by Kishimoto and coworkers [93], miRNA-21 markedly declined after surgery.…”

Section: Micrornas As Biomarkersmentioning

confidence: 99%

See 1 more Smart Citation

Deregulated MicroRNAs in Biliary Tract Cancer: Functional Targets and Potential Biomarkers

Mayr

Beyreis

Wagner

et al. 2016

BioMed Research International

View full text Add to dashboard Cite

Biliary tract cancer (BTC) is still a fatal disease with very poor prognosis. The lack of reliable biomarkers for early diagnosis and of effective therapeutic targets is a major demanding problem in diagnosis and management of BTC. Due to the clinically silent and asymptomatic characteristics of the tumor, most patients are diagnosed at an already advanced stage allowing only for a palliative therapeutic approach. MicroRNAs are small noncoding RNAs well known to regulate various cellular functions and pathologic events including the formation and progression of cancer. Over the last years, several studies have shed light on the role of microRNAs in BTC, making them potentially attractive therapeutic targets and candidates as biomarkers. In this review, we will focus on the role of oncogenic and tumor suppressor microRNAs and their direct targets in BTC. Furthermore, we summarize and discuss data that evaluate the diagnostic power of deregulated microRNAs as possible future biomarkers for BTC.

show abstract

“…51 showed that miR‐21 plays an important role in the regulation of cell proliferation and tumour growth in ICC, in which miR‐21 could also serve as a diagnostic and prognostic marker as well as a potential therapeutic target. They found that miR‐21 levels were significantly higher in serum of ICC patients.…”

Section: Up‐regulated Mirnas In Intrahepatic Cholangiocarcinomamentioning

confidence: 99%

The role of microRNAs in intrahepatic cholangiocarcinoma

Shen

Chan

et al. 2016

J Cellular Molecular Medi

View full text Add to dashboard Cite

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy with poor prognosis. Despite improvements in its diagnosis and therapy, the prognosis for ICC patients remains poor. An improved understanding of ICC pathogenesis and consequential identification of novel therapeutic targets would improve the prognosis of ICC patients. MicroRNAs (miRNAs) are a class of highly conserved, endogenous, small non‐coding RNA molecules of 18–23 nucleotides in length, which regulate gene expression through complementary base‐pairing with target messenger RNAs and subsequent gene silencing. Several studies have shown deregulated expression of miRNAs in ICC cell lines and tissues, in which these miRNAs play important roles in ICC apoptosis, cell proliferation, invasion, migration and metastasis. In this review, we illustrate the potential role of miRNA in the pathogenesis of ICC and explore the possibilities of using miRNAs as prognostic and diagnostic markers, as well as therapeutic targets in ICC.

show abstract

MiR-21 promotes intrahepatic cholangiocarcinoma proliferation and growth in vitro and in vivo by targeting PTPN14 and PTEN

Cited by 99 publications

References 51 publications

miR-191 Inhibition Induces Apoptosis Through Reactivating Secreted Frizzled-Related Protein-1 in Cholangiocarcinoma

miR-191 Inhibition Induces Apoptosis Through Reactivating Secreted Frizzled-Related Protein-1 in Cholangiocarcinoma

Deregulated MicroRNAs in Biliary Tract Cancer: Functional Targets and Potential Biomarkers

The role of microRNAs in intrahepatic cholangiocarcinoma

Contact Info

Product

Resources

About