TIMM50 promotes tumor progression via ERK signaling and predicts poor prognosis of non‐small cell lung cancer patients

Abstract

TIMM50 (Translocase of the inner mitochondrial membrane 50), also called TIM50, plays an essential role in mitochondrial membrane transportation. The existing literature suggests that TIMM50 may perform as an oncogenetic protein in breast cancer. However, the molecular mechanism, especially in human non‐small cell lung cancer (NSCLC), is uncertain to date. In the present study, using immunohistochemistry, we found that TIMM50 expression significantly correlated with larger tumor size (P = 0.049), advanced TNM stage (P = 0.001), positive regional lymph node metastasis (P = 0.007), and poor overall survival (P = 0.001). Proliferation and invasion assay showed that TIMM50 dramatically promoted the ability of proliferation and invasion of NSCLC cells. Subsequent Western blotting results revealed that TIMM50 enhanced the expression of Cyclin D1 and Snail, and inhibited the expression of E‐cadherin. Moreover, TIMM50 facilitated the expression of phosphorylated ERK and P90RSK. Incorporation of ERK inhibitor counteracted the upregulating expression of CyclinD1, and Snail, and downregulating expression of E‐cadherin expression induced by TIMM50 overexpression. In conclusion, our data indicated that TIMM50 facilitated tumor proliferation and invasion of NSCLC through enhancing phosphorylation of its downstream ERK/P90RSK signaling pathway. We speculated that TIMM50 might be a useful prognosis marker of NSCLC patients.

Long non‐coding RNA LOC100133669 promotes cell proliferation in oesophageal squamous cell carcinoma

“…Furthermore, downregulation of Tim50 expression inhibited the growth and chemoresistance of human lung and breast cancer cells harbouring mutant p53 . More recently, Tim50 was reported to facilitate NSCLC cell proliferation and invasion via ERK signalling pathway . In our study, knockdown of LOC100133669 downregulated the protein level of Tim50 through promoting its ubiquitination.…”

“…38 More recently, Tim50 was reported to facilitate NSCLC cell proliferation and invasion via ERK signalling pathway. 39 In our study, knockdown of LOC100133669 downregulated the protein level of Tim50 through promoting its ubiquitination. Cytoplasmic lncRNAs have been reported to participate in regulating protein stability via ubiquitination.…”

“…One of the tein into mitochondria [35][36][37] and has been reported to be involved in tumorigenesis. 38,39 The interaction between LOC100133669…”

Mitochondrial protein import dysfunction: mitochondrial disease, neurodegenerative disease and cancer

“…Overexpression of cyclin D1 has been linked to the progression of a number of different cancers through activation of cellular proliferation [230]. Zhang et al, (2019) demonstrated that treatment of cells with an ERK inhibitor U0126 reversed both Tim50 and cyclin D1 overexpression [194], however it is unclear how the overexpression of Tim50 regulate either cyclin D1 or phosphorylated ERK.…”

Prognostic Value and Related Regulatory Networks of MRPL15 in Non-Small-Cell Lung Cancer

“…Jandee Lee et al illustrated that expression of MRPL44 (components of MRPs) was significantly related to lymph node metastasis and influenced OXPHOS in papillary thyroid cancers (PTCs) (46). Furthermore, reduced mitochondrial respiratory chain activity caused by mtDNA decreased promote metastasis and increased glycolysis in lung cancer cells (47,48). Therefore, we suppose that MRPL15 might impact OXPHOS function and induce poor prognosis.…”