PSMC6 (Proteasome 26S Subunit, ATPase 6)

The nomogram constructed by ER score and clinical features showed good predictive performance on LUAD. This study provided new insights into understanding the role of ER stress in LUAD.

These findings demonstrate, for the first time, that METTL14 modulates the expression of genes related to TNF, IFN, IL, and MHC class I in NPC, proposing a novel role for METTL14 in linking inflammation with cancer, a function that has not been fully elucidated.

Our findings demonstrate that SYT4 is a critical driver of GC progression via activation of the Wnt/β-catenin pathway. Moreover, we uncovered a novel mechanism by which borussertib selectively inhibits SYT4's oncogenic activity, providing compelling evidence for its therapeutic potential in gastric cancer treatment.

ColonTrack effectively distinguishes CRC from non-CRC cases and identifies early-stage CRC with high accuracy (combined area under the curve [AUC] >0.97, sensitivity ∼0.94, specificity ∼0.93). Our analysis of EV protein profiles from tissue and plasma demonstrates ColonTrack's potential as a robust non-invasive biomarker panel for CRC diagnosis and early detection.

Since PSMC6 knockdown did not change sensitivity to 20S and 19S proteasome inhibitors, we suggest a new mode of proteasome targeting by interference with a proteasome ATPase. Overall, a link between PSMC6 and ovarian carcinoma aggressiveness is envisioned, highlighting PSMC6 as a potential diagnostic and therapeutic target.

The functional experiment revealed that KTN1 promotes the proliferation and metastasis of HNSC cells. The pan-cancer analysis of KTN1 revealed its significance in different cancers, which provides a new marker for the diagnosis and prognosis of cancers.

Finally, immunotherapy and chemotherapy may be beneficial to the high-PMRS group based on the immunotherapy cohorts and low half-maximal inhibitory concentration (IC50) values. We identified distinct polyamine modification patterns and established a PMRS to provide new insights into the mechanism of polyamine action and improve the current anti-tumor strategy of LUAD.

PSMC2 overexpression increases chymotrypsin-like proteasome activity at baseline in U266 and ARH77 cells with a similar effect of residual proteasome activity after challenge with bortezomib or carfilzomib. Taken together, our results suggest PSMC2 overexpression correlates with reduced OS in MM patients treated with bortezomib and that PSMC2 may represent an actionable therapeutic target to prevent or overcome PI resistance. PSMC2 overexpression increases proteasome activity in MM cells, mitigates ER stress on PI challenge and promotes PI resistance. mitigates ER stress upon PI challenge, and portending poorer clinical prognosis and more drug resistance, suggesting that 19S targeted agents may help overcome drug resistance in MM.

Multivariate logistic analysis showed that PSMC6 (OR=16.537, 95%CI:2.928-93.393, P=0.001) could be used as an independent risk factor for predicting lymph node metastasis. PSMC6 may be used as a potential molecular marker for judging lymph node metastasis in patients with PCa.

We postulated that the expression of clinically relevant proteasome subunits from MM cells correlated with reduced progression-free survival (PFS) and OS. We correlated the expression of proteasome genes with clinical outcomes using the APEX trial dataset, which compared the effect of bortezomib vs. steroid, and the MMRF COMMPASS trial...These cells exhibit higher levels of proteasome chymotrypsin-like activity activity (1.6-fold increase in ARH77 and 3-fold increase in U266 cells compared to controls; p< 0.01)... Taken together, our results demonstrate that PSMC2 and PSMC6 expression correlates with reduced OS in MM patients. Knockout of PSMC subunits decreased proteasome activity and increased dependence on autophagy, while PSMC upregulation increased proteasome activity and decreased PI sensitivity. Our work highlights the complex interplay of proteasome subunits in MM biology and suggests a prognostic and therapeutic role for 19S RP subunits in the anti-myeloma armamentarium.

PSMC2 and PSMC6 overexpressing cells were also resistant to PI challenge (bortezomib LD50 of 30 nM vs 15 nM in U266 overexpressed and control, bortezomib LD50 of 18 nM vs 10 nM in ARH77 overexpressed vs control cells)... Our results demonstrate that elevated PSMC2 and PSMC6 expression correlates with reduced OS in MM. PSMC subunit inactivation decreased proteasome activity and increased dependence on autophagy, while PSMC upregulation increased proteasome activity and reduced PI sensitivity. Proteasome ATPases are actionable targets with a prognostic and therapeutic role in the armamentarium for MM.

Comparing to C1 subgroup, the patients in C2 subgroup had favorable clinical outcomes, increased immune cells infiltration, and effective immunotherapy response. This study identified polyamines metabolism-associated gene signatures for predicting the patients' survival, and they were also linked to immune cells infiltration and immunotherapy response in LUAD patients.