Overexpression of PSMC2 promotes the tumorigenesis and development of human breast cancer via regulating plasminogen activator urokinase (PLAU)

AbstractEmerging evidence has declared that Proteasome 26S subunit ATPase 2 (PSMC2) is involved in tumor progression. However, its role in breast cancer has not been investigated. Therefore, we sought to establish a correlation between breast cancer and PSMC2. PSMC2 expression in tissues was detected by immunohistochemistry. Loss-of-function study was used to evaluate the effects of PSMC2 knockdown in cell proliferation, apoptosis and migration. A gene microarray was performed to explore the potential downstream of PSMC2 with the help of Ingenuity Pathway Analysis (IPA). The effects of the PSMC2/PLAU axis on breast cancer were examined in vitro. Compared to para-cancer tissues, PSMC2 level was considerably elevated in breast cancer, which was significantly correlated with tumor grade. Knockdown of PSMC2 suppressed breast cancer progression in vitro and in vivo. The mechanistic research revealed that PSMC2 promotes the development and progression of human breast cancer through interacting with PLAU. Outcomes of our study showed that overexpression of PSMC2 provide tumorigenic and metastatic advantages in breast cancer, which may involve the regulation of PLAU. This study not only reveals a critical mechanism of breast cancer development, but also provides a promising therapeutic target for breast cancer treatment.

Download Full-text

tRNA Queuosine Modification Enzyme Modulates the Growth and Microbiome Recruitment to Breast Tumors

Cancers ◽

10.3390/cancers12030628 ◽

2020 ◽

Vol 12 (3) ◽

pp. 628

Author(s):

Jilei Zhang ◽

Rong Lu ◽

Yongguo Zhang ◽

Żaneta Matuszek ◽

Wen Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Human Breast Cancer Cells ◽

Human Breast ◽

And Migration

Background: Transfer RNA (tRNA) queuosine (Q)-modifications occur specifically in 4 cellular tRNAs at the wobble anticodon position. tRNA Q-modification in human cells depends on the gut microbiome because the microbiome product queuine is required for its installation by the enzyme Q tRNA ribosyltransferase catalytic subunit 1 (QTRT1) encoded in the human genome. Queuine is a micronutrient from diet and microbiome. Although tRNA Q-modification has been studied for a long time regarding its properties in decoding and tRNA fragment generation, how QTRT1 affects tumorigenesis and the microbiome is still poorly understood. Results: We generated single clones of QTRT1-knockout breast cancer MCF7 cells using Double Nickase Plasmid. We also established a QTRT1-knockdown breast MDA-MB-231 cell line. The impacts of QTRT1 deletion or reduction on cell proliferation and migration in vitro were evaluated using cell culture, while the regulations on tumor growth in vivo were evaluated using a xenograft BALB/c nude mouse model. We found that QTRT1 deficiency in human breast cancer cells could change the functions of regulation genes, which are critical in cell proliferation, tight junction formation, and migration in human breast cancer cells in vitro and a breast tumor mouse model in vivo. We identified that several core bacteria, such as Lachnospiraceae, Lactobacillus, and Alistipes, were markedly changed in mice post injection with breast cancer cells. The relative abundance of bacteria in tumors induced from wildtype cells was significantly higher than those of QTRT1 deficiency cells. Conclusions: Our results demonstrate that the QTRT1 gene and tRNA Q-modification altered cell proliferation, junctions, and microbiome in tumors and the intestine, thus playing a critical role in breast cancer development.

Download Full-text

Expression of protein tyrosine phosphatase alpha (RPTPα) in human breast cancer correlates with low tumor grade, and inhibits tumor cell growth in vitro and in vivo

Oncogene ◽

10.1038/sj.onc.1203869 ◽

2000 ◽

Vol 19 (43) ◽

pp. 4979-4987 ◽

Cited By ~ 52

Author(s):

Elena Ardini ◽

Roberto Agresti ◽

Elda Tagliabue ◽

Marco Greco ◽

Piera Aiello ◽

...

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Protein Tyrosine Phosphatase ◽

Human Breast Cancer ◽

Tyrosine Phosphatase ◽

Tumor Grade ◽

Tumor Cell Growth ◽

Human Breast

Download Full-text

Regulation of autophagy by microRNAs in human breast cancer

Journal of Biomedical Science ◽

10.1186/s12929-021-00715-9 ◽

2021 ◽

Vol 28 (1) ◽

Author(s):

Zhi Xiong Chong ◽

Swee Keong Yeap ◽

Wan Yong Ho

Keyword(s):

Breast Cancer ◽

Treatment Response ◽

Cancer Progression ◽

Mammalian Cells ◽

Human Breast Cancer ◽

Solid Cancer ◽

Human Breast ◽

Female Population

AbstractBreast cancer is the most common solid cancer that affects female population globally. MicroRNAs (miRNAs) are short non-coding RNAs that can regulate post-transcriptional modification of multiple downstream genes. Autophagy is a conserved cellular catabolic activity that aims to provide nutrients and degrade un-usable macromolecules in mammalian cells. A number of in vitro, in vivo and clinical studies have reported that some miRNAs could modulate autophagy activity in human breast cancer cells, and these would influence human breast cancer progression and treatment response. Therefore, this review was aimed to discuss the roles of autophagy-regulating miRNAs in influencing breast cancer development and treatment response. The review would first introduce autophagy types and process, followed by the discussion of the roles of different miRNAs in modulating autophagy in human breast cancer, and to explore how would this miRNA-autophagy regulatory process affect the disease progression or treatment response. Lastly, the potential applications and challenges of utilizing autophagy-regulating miRNAs as breast cancer biomarkers and novel therapeutic agents would be discussed.

Download Full-text

The effects of naloxone on human breast cancer progression: in vitro and in vivo studies on MDA.MB231 cells

OncoTargets and Therapy ◽

10.2147/ott.s145780 ◽

2018 ◽

Vol Volume 11 ◽

pp. 185-191 ◽

Cited By ~ 6

Author(s):

Sabrina Bimonte ◽

Antonio Barbieri ◽

Marco Cascella ◽

Domenica Rea ◽

Giuseppe Palma ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Human Breast Cancer ◽

Breast Cancer Progression ◽

In Vivo Studies ◽

Human Breast

Download Full-text

tRNA queuosine modification enzyme modulates the growth and microbiome recruitment to breast tumors

10.21203/rs.2.21087/v1 ◽

2020 ◽

Author(s):

Jilei Zhang ◽

Rong Lu ◽

Yong-Guo Zhang ◽

Żaneta Matuszek ◽

Yinglin Xia ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Mouse Model ◽

Human Breast Cancer ◽

Cancer Development ◽

Human Breast ◽

Mcf7 Cells ◽

And Migration

Abstract Background: Transfer RNA (tRNA) queuosine (Q)-modifications occur specifically in 4 cellular tRNAs at the wobble anticodon position. tRNA Q-modification in human cells depends on the gut microbiome because the microbiome product queuine is required for its installation by the enzyme queuine tRNA ribosyltransferase catalytic subunit 1 (QTRT1) encoded in the human genome. Although tRNA Q-modification has been studied a long time regarding its properties in decoding and tRNA fragment generation, how QTRT1 affects tumorigenesis is still poorly understood. Results: We generated single clones of QTRT1-knockout breast cancer MCF7 cells using Double Nickase Plasmid. The impacts of QTRT1-delection on cell proliferation and migration in vitro were evaluated using cell culture, while the regulations on tumor growth in vivo were evaluated using xenograft BALB/c nude mouse model. We found that QTRT1 completely deleted from human breast cancer MCF7 cells could change the functions of regulation genes which are critical in cell proliferation, tight junction formation, and migration in human breast cancer cells in vitro and a breast tumor mouse model in vivo . We also found that microbiome maybe involved in the breast cancer development in vivo. Conclusions: Our results demonstrate that the QTRT1 gene and microbiome play a critical role in breast cancer development.

Download Full-text