, KRT17 knockdown inhibited in vivo tumor growth. KRT17 knockdown induced dysregulation of ERK1/2 and upregulation of the pro-apoptotic Bcl-2 protein Bad. In conclusion, the present study demonstrated that elevated KRT17 levels are positively associated with pancreatic cancer progression; KRT17 knockdown suppressed cell growth, colony formation, migration and tumor growth, and induced apoptosis and cell cycle arrest, affecting ERK1/2/Bad signaling. Therefore, the results of the present study suggested that KRT17 may be a potential target for the treatment of pancreatic cancer.
Background. Interleukin-2 (IL-2) is proved to play an irreplaceable role in antitumor regulation in numerous experimental and clinical trials. Tumor-associated macrophages (TAMs) are able to release exosomes to promote the development and progression of hepatocellular carcinoma (HCC) as essential component of microenvironment. In this study, our intention is to explore the effects of the exosomes from TAMs with IL-2 treatment on HCC development. TAMs were collected and cultured from HCC tissues. The exosomes from the TAMs treated with IL-2 (ExoIL2-TAM) or not (ExoTAM) were identified and used to treat HCC cells in vivo and in vitro. The proliferation, apoptosis, and metastasis of HCC cells were measured. The changes of miRNAs in exosomes were explored to clarify the possible mechanisms. Both decrease of cell proliferation and metastasis and increase of apoptosis were observed with ExoIL2-TAM treatment compared with ExoTAMin vivo and in vitro. miR-375 was obviously augmented in ExoIL2-TAM and HCC cells treated with ExoIL2-TAM. Taken together, IL-2 may modulate exosomal miRNAs from TAMs to ameliorate hepatocellular carcinoma development. This study provides a new perspective to explain the mechanism by which IL-2 inhibits hepatocellular carcinoma and implies the potential clinical value of exosomal miRNAs released by TAMs.
Background:
The Hippo pathway's primary kinase component, large tumor suppressor 1 (LATS1), has been hypothesized as a tumor suppressor in a variety of cancers. LATS1's biological effects on colorectal cancer (CRC) are yet to be determined.
Methods:
The analysis of LATS1 mRNA expression in CRC was conducted using public databases from the Gene Expressing Profiling Interactive Analysis database (GEPIA). Investigation for the expression of LATS1 protein in 102 CRC tumor tissues and 57 normal tissues was performed using immunohistochemistry (IHC) analysis.
In vitro
genetic manipulation was used to explore the potential role and mechanism of LATS1 in the regulation of proliferation and migration of CRC cells.
Results:
LATS1 was found to be considerably downregulated in CRC tissues, with much lower levels in individuals with bigger tumors of size (≥5 cm), deeper invasion (T3-4), positive lymph node metastasis (LNM), and advanced tumor-node-metastasis (TNM) stage (III-IV). As exhibited by clinical data analysis, LATS1 loss was significantly associated with TNM and LNM staging in CRC patients. Furthermore, our
in vitro
investigations revealed that LATS1 depletion increased CRC cell proliferation and migration in HCT116 cells, whereas overexpressing LATS1 had the opposite effect in SW620 cells. LATS1 suppressed the expression of glioma-associated oncogene-1 (Gli1), and LATS1's tumor-suppressive actions in CRC are dependent on Gli1. Moreover, LATS1 could modulate Yes-associated protein 1 (YAP1) expression and mTOR activation in CRC cells.
Conclusion:
Our findings identify the LATS1 as a unique Gli1 regulator in CRC cell migration and proliferation, and suggest that LATS1 may serve as a potential therapeutic target for CRC.
It is crucial to probe into the biological effect and mechanism of miRNA-485-5p regulating KRT17 in pancreatic cancer (PC) to understand its pathogenesis and identify potential biological targets. The bioinformatics means were used to evaluate the clinical significance of KRT17 expression in the TCGA database. TargetScan database analysis in conjunction with dual luciferase and RNA Immunoprecipitation (RIP) experiments was used to probe the interaction relationship of miRNA-485-5p with KRT17. The expression of miRNA-485-5p and KRT17 in PC tissue and cancer cell lines was detected by Q-PCR paired with western blot assay. The biological function of miRNA-485-5p in regulating KRT17 was investigated in the PC cell line via gene silencing/overexpression technique. A western blot experiment was utilized to investigate the regulatory effect of KRT17 on cell cycle-related proteins and the FAK/Src/ERK signal pathway. The level of KRT17 was dramatically increased in PC tissues and this significantly decreased the survival rate of PC patients. TargetScan in combination with dual luciferase and RIP experiments verified the miRNA-485-5p target KRT17. The expression of KRT17 was high in the PC cell line, although the expression of miRNA-485-5p was low. Silencing KRT17 or overexpression of miRNA-485-5p significantly inhibited PC cell viability, proliferation, invasion, and colony formation, while promoting apoptosis. In contrast, overexpression of KRT17 drastically reversed the function of miRNA-485-5p. The silenced KRT17 remarkably downregulated the expression of cyclinD1, CDK1, CDK2, p-FAK, p-Src, and p-ERK proteins in the PC cells. Generally, an essential signaling cascade of miRNA-485-5p/KRT17/FAK/Src/ERK influences the biological functions of PC cells.
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