MicroRNA-101-3p suppresses proliferation and migration in hepatocellular carcinoma by targeting the HGF/c-Met pathway

Liu, Yang; Tan, Juan; Ou, Shuangyan; Chen, Limin

doi:10.1007/s10637-019-00766-8

Cited by 22 publications

(14 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of note, the combination of c-Met inhibitors with other related molecule inhibitors would be a promising strategy due to the low sensitivity and effectiveness of single-agent regimens in preclinical and clinical trials. 39,40 More recent studies have identified a set of small molecules against P-Rex1 by differential scanning fluorimetry, but inhibition of P-Rex1-related cell function needs to be further confirmed. 41 Liver cancer is an extraordinarily heterogeneous malignancy with a poor prognosis and a lack of curative treatments that requires continued research efforts.…”

Section: Discussionmentioning

confidence: 99%

<p>Identification of P-Rex1 in the Regulation of Liver Cancer Cell Proliferation and Migration via HGF/c-Met/Akt Pathway</p>

Qiu¹,

Chang²,

Liu³

et al. 2020

OTT

View full text Add to dashboard Cite

Background: Rho-GTPases and their activators, guanine nucleotide exchange factors (GEFs), are increasingly being recognized as essential mediators of oncogenic signaling. Although it is known that P-Rex1, a member of the Dbl family of GEFs for the Rac small GTPase, contributes to the migration of cancer cells, its exact role in liver cancer and the underlying mechanisms remain unclear. Materials and Methods: Public datasets from the Gene Expression Omnibus database (GEO) and clinical liver cancer samples were analyzed to explore the expression of P-Rex1. P-Rex1 knockdown and overexpression cell lines were established using a recombinant lentiviral transfection system. BrdU and colony formation assays were performed to determine cell viability. Migratory capacity was analyzed using a transwell migration assay and an in vitro wound-healing assay. Nude mice bearing subcutaneous xenograft tumors were established to determine the effects of P-Rex1 on tumorigenesis in vivo. The role of P-Rex1 in hepatocarcinogenesis was determined through Western blot and coimmunoprecipitation. Results: Induced expression of endogenous P-Rex1 was identified in liver cancer tumors when compared with adjacent nonmalignant tissues from clinical data. In response to HGF treatment, P-Rex1-knockdown cells displayed reduced proliferation and migration in vitro as well as reduced xenograft tumor growth in vivo. Overexpression of P-Rex1 promoted liver cancer cell proliferation and migration. P-Rex1 primarily acts as a downstream effector of GPCR signaling. This study demonstrated that downregulation of P-Rex1 led to a significant decrease in the phosphorylation of Akt and Erk1/2 by reducing the phosphorylation of the tyrosine kinase receptor c-Met. Furthermore, a physical association between P-Rex1 and c-Met was observed after HGF treatment, suggesting that P-Rex1 may be involved in the HGF/c-Met signaling pathway. Conclusion: These results support the role of P-Rex1 as a novel player in liver cancer, which suggest that targeting P-Rex1 may provide a potential strategy for liver cancer treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

<p>Identification of P-Rex1 in the Regulation of Liver Cancer Cell Proliferation and Migration via HGF/c-Met/Akt Pathway</p>

Qiu¹,

Chang²,

Liu³

et al. 2020

OTT

View full text Add to dashboard Cite

show abstract

“…Herein, we mainly focus on the role of miRNAs in HCC. For example, miR-101 suppresses the proliferation and migration of HCC cells and tumors through targeting HGF/c-Met, Girdin, SOX9 and TGF-β in in vitro and in vivo trials (Cao et al, 2016;Yang et al, 2016;Yan et al, 2018;Liu et al, 2019). miRNA-206 targets c-Met and cyclin-dependent kinase 6 (Cdk6) to suppress development of HCC in mice (Wu et al, 2017).…”

Section: Micrornasmentioning

confidence: 99%

The Function of the HGF/c-Met Axis in Hepatocellular Carcinoma

Rao

Lou

et al. 2020

Front. Cell Dev. Biol.

121

100

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, leading to a large global cancer burden. Hepatocyte growth factor (HGF) and its highaffinity receptor, mesenchymal epithelial transition factor (c-Met), are closely related to the onset, progression, and metastasis of multiple tumors. The HGF/c-Met axis is involved in cell proliferation, movement, differentiation, invasion, angiogenesis, and apoptosis by activating multiple downstream signaling pathways. In this review, we focus on the function of the HGF/c-Met axis in HCC. The HGF/c-Met axis promotes the onset, proliferation, invasion, and metastasis of HCC. Moreover, it can serve as a biomarker for diagnosis and prognosis, as well as a therapeutic target for HCC. In addition, it is closely related to drug resistance during HCC treatment.

show abstract

“…Various miRNAs, including let-7, miR-34a and the miR-200 family, have been identified as potential biomarkers or therapeutic molecules ( 3 ). Previous studies have reported that miR-101 is downregulated in various types of cancer and suppresses cancer cell progression, such as bladder cancer ( 4 ), breast cancer ( 5 ), hepatocellular carcinoma ( 6 ) and CRC ( 7 ). However, the comprehensive mechanisms underlying the effects of miR-101 on CRC progression have not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑101 suppresses colorectal cancer progression by negative regulation of Rap1b

Zhou

Duan

et al. 2020

Oncol Lett

View full text Add to dashboard Cite

Colorectal cancer (CRC) is the fourth most lethal malignancy and is the second most common cause of cancer-associated mortality worldwide. The development of high-throughput sequencing has enabled the identification of potential biomarkers for the diagnosis and treatment of various types of cancer. Although microRNA-101 (miR-101) has been demonstrated to be a potential biomarker of CRC, its detailed mechanisms remain to be fully discovered. In the present study, overall survival analysis was applied to determine the association between miR-101 and CRC prognosis. Reverse transcription-quantitative PCR (RT-qPCR) was used to examine gene expression levels in tissues and cells. Cell proliferative and apoptotic activities were determined by MTT and flow cytometry assays, respectively. Wound healing and Transwell assays were used to examine CRC cell migration and invasion, respectively. In the present study, RT-qPCR analysis indicated that miR-101 was significantly downregulated in CRC tissues and cells. However, clinical data collected from The Cancer Genome Atlas revealed no significant association between the expression levels of miR-101 and the prognosis of CRC. Additionally, miR-101 inhibited the progression of CRC by directly binding to the 3'-untranslated region of Ras-related protein Rap1b (Rap1b). This was associated with downregulation of Rap1b expression. Furthermore, the overexpression of Rap1b promoted miR-101 mimic-attenuated CRC cell progression. The present study demonstrated that miR-101 may be involved in the repression of the CRC progression by forming a negative feedback loop with Rap1b. The findings revealed the interaction between miR-101 and Rap1b during the progression of CRC, which could aid the development of therapeutic strategies.

show abstract

MicroRNA-101-3p suppresses proliferation and migration in hepatocellular carcinoma by targeting the HGF/c-Met pathway

Cited by 22 publications

References 35 publications

<p>Identification of P-Rex1 in the Regulation of Liver Cancer Cell Proliferation and Migration via HGF/c-Met/Akt Pathway</p>

<p>Identification of P-Rex1 in the Regulation of Liver Cancer Cell Proliferation and Migration via HGF/c-Met/Akt Pathway</p>

The Function of the HGF/c-Met Axis in Hepatocellular Carcinoma

MicroRNA‑101 suppresses colorectal cancer progression by negative regulation of Rap1b

Contact Info

Product

Resources

About