Chaperone protein l-isoaspartate (d-aspartyl) O-methyltransferase as a novel predictor of poor prognosis in lung adenocarcinoma

Saito, Heisuke; Yamashita, Masahiro; Ogasawara, Masahito; Yamada, Noriyuki; Niisato, Miyuki; Tomoyasu, Makoto; Deguchi, Hiroyuki; Tanita, Tatsuo; Ishida, Kazuyuki; Sugai, Tamotsu; Yamauchi, Kohei

doi:10.1016/j.humpath.2015.11.006

Cited by 18 publications

(17 citation statements)

References 28 publications

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“…The prognostic value of PCMT1 has been reported in lung cancer and breast cancer . Saito et al indicated that PCMT1 overexpression was a predictive biomarker of unfavorable prognosis for surgically resected lung adenocarcinoma . Lee et al demonstrated that the survival of breast cancer patients exhibiting higher‐expression of PCMT1 was significantly poorer than those with lower expression of PCMT1 .…”

Section: Discussionmentioning

confidence: 99%

“…Human PCMT1 is 24.5 kDa monomeric enzyme that is comprised of two isoforms resulting from alternative splicing . In lung adenocarcinoma, PCMT1 expression was significantly lower in patients with stage I or preinvasive lesions than in those with stage II–IV or invasive adenocarcinoma . The expression status of PCMT1 in bladder cancer is still unknown.…”

Section: Introductionmentioning

confidence: 99%

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PCMT1 is an unfavorable predictor and functions as an oncogene in bladder cancer

Dong

Xue

et al. 2018

IUBMB Life

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The role of protein l-isoaspartate (d-aspartate) O-methyltransferase (PCMT1) in human cancer was generally cognized. The clinical significance and biological function of PCMT1 in bladder cancer is still unknown. PCMT1 mRNA and protein expression levels in bladder cancer tissues and cell lines were detected by qRT-PCR, immunohistochemistry, or western blot. The correlation between PCMT1 expression and clinicopathological factors was analyzed through immunohistochemistry in 108 bladder cancer patients. Loss-of-function and gain-of-function studies were conducted to explore the biological function of PCMT1 in bladder cancer cell lines in regulating cell proliferation, migration, and invasion. In our results, we found that PCMT1 was overexpressed in bladder cancer tissues compared with normal urothelium tissues in microarray datasets (GSE3167). Then, we confirmed PCMT1 mRNA and protein expression were increased in bladder cancer tissues and cell lines compared with paired normal urothelium tissues and normal uroepithelial cell line. PCMT1 protein expression was obviously correlated with clinical stage, muscularis invasion, lymph node metastasis, and distant metastasis. Survival analysis showed that PCMT1 protein high-expression was an independent unfavorable prognostic factor for bladder cancer patients. The in vitro experiments showed PCMT1 regulated bladder cancer cells migration and invasion through modulating epithelial-mesenchymal transition (EMT)-associated genes expression including E-cadherin, vimentin, Snail and Slug, but had no effect on proliferation. In conclusion, PCMT1 is an unfavorable prognostic biomarker and involves in cells migration and invasion through regulating EMT-associated genes. © 2018 IUBMB Life, 70(4):291-299, 2018.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

PCMT1 is an unfavorable predictor and functions as an oncogene in bladder cancer

Dong

Xue

et al. 2018

IUBMB Life

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“…Lung cancer (LC) is the leading cause of cancer‐related mortality worldwide, with lung adenocarcinoma (LUAD) being the most frequently diagnosed histological subtype . Most patients with LUAD are usually diagnosed at advanced stages and have a poor prognosis . It is therefore necessary to define new molecular biomarkers for the early diagnosis of LUAD.…”

Section: Introductionmentioning

confidence: 99%

miR‐15b enhances the proliferation and migration of lung adenocarcinoma by targeting BCL2

et al. 2020

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Background: Lung adenocarcinoma (LUAD) is a subtype of lung cancer (LC), which is the most common tumor worldwide. Accumulating evidence has elucidated an important role of microRNAs (miRNAs) in mediating the development and progression of several tumors. The purpose of this study was to explore the role and underlying mechanism of miR-15b in LUAD. Methods: CCK-8 and Transwell assays were conducted to measure the capacities of cell viability and migration in SPC-A1 cells. Luciferase assay was utilized to verifymiR-15b direct binding to BCL2 mRNA 3 0 -UTR. Results: We determined that miR-15b was overexpressed in LUAD and miR-15b overexpression predicted a significantly worse outcome in patients with LUAD. miR-15b improved LUAD growth in vitro and vivo. miR-15b enhanced cell migration and epithelial-mesenchymal transition (EMT) in LUAD. miR-15b promoted cell viability, migration and EMT through inhibiting BCL2 expression by targeting to its mRNA 3 0 -UTR. BCL2 reversed functions of miR-15b on promoting cell proliferation, migration and EMT in SPC-A1 cells. Conclusions: miR-15b promoted cell viability, migration and EMT by targeting BCL2 in LUAD. The newly identified miR-15b/BCL2 axis provides a novel insight into the pathogenesis of LUAD.

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“…Recently, concern has increased regarding the pathogenic association between cancer and protein L-isoaspartyl (D-aspartyl) O- methyltransferase (PIMT), which functions as a chaperone for the conversion of isomerized L-isoaspartyl and D-aspartic acid residues into L–Asp [ 10 – 13 ]. Lapointe et al found that expression levels of PIMT are inversely correlated with stage progression in astrocytic tumors [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…They demonstrated mutual interference between PIMT and wild-type p53 expression in vitro using various cell lines, and found that inductive expression of PIMT exerts an anti-apoptotic and carcinogenic effect by inhibiting the wild-type p53 pathway. We previously reported that strong expression of PIMT was immunohistochemically detected in approximately half of patients with lung adenocarcinoma and an independent predictor of poor prognosis for lung adenocarcinoma [ 13 ]. In addition, strong PIMT expression was correlated with higher levels of 78-kDa glucose-regulated protein (GRP78), a marker of ER stress, rather than p53 expression.…”

Section: Introductionmentioning

confidence: 99%

Deficiency of protein-L-isoaspartate (D-aspartate) O-methyl-transferase expression under endoplasmic reticulum stress promotes epithelial mesenchymal transition in lung adenocarcinoma

et al. 2018

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A prognostic association between the novel chaperone protein-L-isoaspartate (D-aspartate) O-methyltransferase (PIMT) and lung adenocarcinoma has recently been reported. Here, we evaluated the functional roles of PIMT in the progression of lung adenocarcinoma. PIMT expression was detectable in 6 lung adenocarcinoma cell lines: A549, H441, H460, H1650, Calu 1, and Calu 6 cell lines. In A549 and H441 cells, knockdown by PIMT using silencing RNA of PIMT (si-PIMT) and/or small hairpin-RNA (sh-PIMT) induced a decrease in the expression of E-cadherin with an increase in vimentin expression, indicating that the epithelial to mesenchymal transition (EMT) was induced. Cell mobility, including migration and invasion capability, was increased in sh-PIMT A549 stable and si-PIMT H441 cells compared to in control cells. Endoplasmic reticulum (ER) stress, such as Thapsigargin (Tg) stress and hypoxia, induced EMT in A549 cells but not in other cell types, with an increase in GRP78 expression, whereas overexpression of PIMT reduced the EMT and cell invasion under stress conditions. The expression of hypoxia inducible factor-1 alpha (HIF1α) and Twist increased in sh-PIMT A549 and si-PIMT H441 cells, and Tg stress increased HIF1α expression levels in A549 cells in a dose-dependent manner. Moreover, LW6, an HIF1α inhibitor, reduced EMT, cancer invasion, and the levels of Twist in sh-PIMT A549 cells. Our results indicate that deficiency of supplemental PIMT expression under ER stress facilitates EMT and cell invasion in some cell types of lung adenocarcinoma.

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Chaperone protein l-isoaspartate (d-aspartyl) O-methyltransferase as a novel predictor of poor prognosis in lung adenocarcinoma

Cited by 18 publications

References 28 publications

PCMT1 is an unfavorable predictor and functions as an oncogene in bladder cancer

PCMT1 is an unfavorable predictor and functions as an oncogene in bladder cancer

miR‐15b enhances the proliferation and migration of lung adenocarcinoma by targeting BCL2

Deficiency of protein-L-isoaspartate (D-aspartate) O-methyl-transferase expression under endoplasmic reticulum stress promotes epithelial mesenchymal transition in lung adenocarcinoma

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