RETRACTED: Mitochondrial-Associated Protein LRPPRC is Related With Poor Prognosis Potentially and Exerts as an Oncogene Via Maintaining Mitochondrial Function in Pancreatic Cancer

Abstract

Background: The mitochondrial-associated protein leucine-rich pentatricopeptide repeat-containing (LRPPRC) exerts multiple functions involved in physiological processes, including mitochondrial gene translation, cell cycle progression, and tumorigenesis. Previously, LRPPRC was reported to regulate mitophagy by interacting with Bcl-2 and Beclin-1 and thus modifying the activation of PI3KCIII and autophagy. Considering that LRPPRC was found to be negatively associated with survival rate, we hypothesize that LRPPRC may be involved in pancreatic cancer progression via its regulation of autophagy.Methods: Real-time quantitative polymerase chain reaction was performed to detect the expression of LRPPRC in 90 paired pancreatic cancer and adjacent tissues and five pancreatic cancer cell lines. Mitochondrial reactive oxidative species level and function were measured. Mitophagy was measured by performing to detect LC3 levels.Results: By performing a real-time quantitative polymerase chain reaction, the association of LRPPRC with the prognosis of pancreatic cancer was established, and pancreatic cancer tissues had significantly higher LRPPRC expression than adjacent tissues. LRPPRC was negatively associated with the overall survival rate. LRPPRC was also upregulated in pancreatic cancer cell lines. Knockdown of LRPPRC promoted reactive oxidative species accumulation, decreased mitochondrial membrane potential, promoted autophagy/mitophagy, and induced mitochondrial dysfunction. Subsequently, knockdown of LRPPRC inhibited malignant behaviors in PANC-1 cells, including proliferation, migration, invasion, tumor formation, and chemoresistance to gemcitabine. Finally, by inhibiting autophagy/mitophagy using 3-MA, the inhibitory effect of LRPPRC knockdown on proliferation was reversed.Conclusion: Taken together, our results indicate that LRPPRC may act as an oncogene via maintaining mitochondrial homeostasis and could be used as a predictive marker for patient prognosis in pancreatic cancer.

M6A Methylation Modification–Mediated Mucosal Immune Microenvironment in Crohn's Disease

“…Its expression is signi cantly higher than that in adjacent tissues, and LRPPRC negatively correlates with overall survival [14]. Knockdown of LRPPRC inhibited the malignant biological behavior of PANC-1 cells, including proliferation and migration [15]. We also show that WTAP plays an essential role in many physiological processes in the cell, including binding to the 3 ′ untranslated region of the mRNA to improve mRNA stability [16].…”

Gossypol acetic acid regulates leukemia stem cells by degrading LRPPRC via inhibiting IL-6/JAK1/STAT3 signaling or resulting mitochondrial dysfunction

“…It is reported that GAA acts as an anti-tumor agent, via targeting to LRPPRC and resulted in protein degradation[ 16 ], we treated KG1a-SCs and Kasumi-1-SCs with GAA with different concentrations ranged from 2.5-10 μmol/L for 24 h. By performing western blot, it is presented that 5-10 μmol/L GAA treatment significantly decreased LRPPRC protein levels after 24 h via promoting protein degradation (Figure 1B ), without affecting LRPPRC transcription (data not shown). By considering that LRPPRC acts as a oncogenic factor in several kinds of cancer[ 18 , 19 ], we then evaluate the effect of GAA on KG1a-SCs and Kasumi-1-SCs cell viability and colony formation. As shown in Figure 1C , GAA treatment ranged from 5-10 μmol/L significantly decreased cell viability.…”

STOML2 Restricts Mitophagy and Increases Chemosensitivity in Pancreatic Cancer through Stabilizing PARL-induced PINK1 degradation

“…For chemoresistance, previous studies suggested that the impaired mitophagy restricted the metabolic plasticity, which made the pancreatic cancer cells susceptible to metformin treatment (40). However, another related research showed that mitophagy could inhibit malignant behaviors including chemoresistance in pancreatic cancer cells (41). Therefore, there remain many controversies between mitophagy and chemoresistance in pancreatic cancer, which deserves further study (42).…”