CNPY2 inhibits MYLIP-mediated AR protein degradation in prostate cancer cells

Zhou

et al. 2020

Aging

The lncRNA tumor suppressor candidate 8 (TUSC8) plays a critical role in the development of several cancers. However, the biological functions and underlying molecular mechanisms of TUSC8 with respect to breast cancer remain largely unclear. Here, we found that TUSC8 was significantly down-regulated in breast cancer tissues and its high expression predicted better prognosis of breast cancer patients. Functionally, knock-down of TUSC8 drastically promoted the proliferation, migration and invasion of breast cancer cells in vitro and facilitated tumorigenicity and metastasis in vivo. Mechanistically, the results of luciferase reporter, RIP and RNA pulldown assays proved that TUSC8 functioned as molecular sponge for miR-190b-5p. Furthermore, we showed that TUSC8 served as a competing endogenous RNA (ceRNA) of myosin regulatory light chain interacting protein (MYLIP) through competitively binding with miR-190b-5p and suppressed breast cancer metastasis through regulating the expression of epithelial-mesenchymal transition (EMT) related markers. Clinically, the receiver operating characteristic curve (ROC) analyses revealed that the combination usage of TUSC8 and MYLIP might become novel promising diagnostic biomarkers for breast cancer. Taken together, these results suggested that TUSC8 inhibited breast cancer growth and metastasis via miR-190b-5p/MYLIP axis, providing us new insights into developing potential therapeutic targets for breast cancer patients.

Section: Discussionsupporting

confidence: 53%

Long non-coding RNA TUSC8 inhibits breast cancer growth and metastasis via miR-190b-5p/MYLIP axis

Zhou

et al. 2020

Aging

“…UBE2O targets AMPKa2 for ubiquitination and degradation and UBE2O blockade inhibits tumorigenesis through AMPKa2 restoration [ 260 ]. Furthermore, MYLIP is an E3 ubiquitin-protein ligase whose activity depends on E2 enzymes of the UBE2D family and that was shown to affect AR activity in prostate cancer [ 172 ].…”

Section: Post-translational Modifications In Prostate Cancermentioning

confidence: 99%

“…prolongs the half-life of the E2F1 protein by inhibiting its ubiquitination (MDM2 displaces SCFSKP2); influences cell proliferation [168] MYCBP2 Atypical E3 ubiquitin-protein ligase, which mediates ubiquitination of threonine and serine, instead of lysine residues AR, MYC [138] Tumorigenicity of AR-positive PCa cells [138] MYLIP E3 ubiquitin-protein ligase whose activity depends on E2 enzymes of the UBE2D family AR [172] AR activity [172] PIRH2 Ring finger protein with ubiquitin ligase activity Epsilon-COP [173]; HDAC1 [174] Regulation of the secretion of PSA [173]; AR signaling [174] pVHL Substrate recognition subunit of the VHL-Elongin B/C E3 ligase complex that targets the HIF-1/2 for proteasomal degradation under normoxia conditions AR (enhanced AR de-ubiquitination instead of inducing AR ubiquitination) [175]; HIF-1α [176] Suppression of AR activity [175]; HIF-1 hypoxic response [176] RNF2 Also known as RING1b or RING2; catalytic subunit of PRC1 TXNIP [177]; CCL2 [178] Cell cycle arrest and apoptosis [177]; metastasis in mice inoculated intracardially with PC-3M cells [178]…”

Section: Mdm2mentioning

confidence: 99%

Post-Translational Modifications That Drive Prostate Cancer Progression

Samaržija

2021

Biomolecules

While a protein primary structure is determined by genetic code, its specific functional form is mostly achieved in a dynamic interplay that includes actions of many enzymes involved in post-translational modifications. This versatile repertoire is widely used by cells to direct their response to external stimuli, regulate transcription and protein localization and to keep proteostasis. Herein, post-translational modifications with evident potency to drive prostate cancer are explored. A comprehensive list of proteome-wide and single protein post-translational modifications and their involvement in phenotypic outcomes is presented. Specifically, the data on phosphorylation, glycosylation, ubiquitination, SUMOylation, acetylation, and lipidation in prostate cancer and the enzymes involved are collected. This type of knowledge is especially valuable in cases when cancer cells do not differ in the expression or mutational status of a protein, but its differential activity is regulated on the level of post-translational modifications. Since their driving roles in prostate cancer, post-translational modifications are widely studied in attempts to advance prostate cancer treatment. Current strategies that exploit the potential of post-translational modifications in prostate cancer therapy are presented.

“…Myosin regulatory light‐chain interacting protein (MYLIP), one of the ubiquitin ligases, has a crucial effect on various cancers such as prostate cancer cells, breast cancer, and cervical cancer. 19 , 20 , 21 In 2020, MYLIP was found to be correlated with poor prognosis when it downregulated in NSCLC. Nevertheless, the mechanism of the above functions has rarely been studied.…”

Section: Introductionmentioning

confidence: 99%

LncRNASGMS1‐AS1 regulates lung adenocarcinoma cell proliferation, migration, invasion, and EMT progression via miR‐106a‐5p/MYLI9 axis

et al. 2021

Background: Lung cancer mainly includes non-small cell lung cancer (NSCLC). Lung adenocarcinoma (LUAD) is the main subtype of NSCLC. Long non-coding RNAs (LncRNAs) had been found to exert numerous functions on the progressions of cancers. MicroRNAs often exist as the target of LncRNAs to regulate a series of signaling pathways in human. We explored the effects and molecular mechanism of LncRNA SGMS1-AS1 on the procedures of LUAD cells. Methods: The ENCORI and GEPIA databases were used to analyze the differences in SGMS1, miR-106a-5p, and MYLIP between LUAD and normal tissue. Their expression levels were examined by RT-PCR. CCK8, colony formation, migration, and invasion assay were conducted in LUAD cells which had silenced SGMS1-AS1. To verify the relationship between SGMS1-AS1, miR-106a-5p, and MYLIP, we overexpressed miR-106a-5p inhibitor or MYLIP in LUAD cells after decreasing SGMS1-AS1 and repeated the above assays. Results: SGMS1-AS1 was downregulated in LUAD tissue as well as cells, which was related to good prognosis of patients with lung adenocarcinoma. Additionally, knockdown of SGMS1-AS1 promoted proliferation, migration, invasion, and epithelial mesenchymal transition (EMT) progression of LUAD cells, which meant that SGMS1-AS1 inhibited the progression of LUAD cells. Furthermore, miR-106a-5p was the direct target of SGMS1-AS1 and transfecting miR-106a-5p inhibitor could reversed the impact induced by knockdown of SGMS1-AS1. Subsequently, we found that MYLIP was the target of miR-106a-5p, which was negatively correlated with miR-106a-5p, but had high positive correlation with SGMS1-AS1. Consistently, overexpression MYLIP partly eliminated the effects on A549 cells induced by silencing of SGMS1-AS1. Conclusion: LncRNA SGMS1-AS1 inhibits the proliferation, invasion, migration and EMT progression of LUAD cells via targeting miR-106a-5p/MYLIP axis.