Inhibition of LDHA suppresses tumor progression in prostate cancer

Zhang, Xian; Liu, Jiumin; Chen, Qing-Ke; Chen, Hanzhong; Ye, Chujin; Xue, Jian; Yang, Huanqing; Li, Jinglei; Liu, Xuefeng; Kuang, Su‐Juan

doi:10.1007/s13277-015-3540-x

Cited by 113 publications

(83 citation statements)

References 18 publications

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“…LDHA catalyzes the conversion of pyruvate to lactate and is considered to be a key checkpoint of anaerobic glycolysis (9). Increased levels of LDHA have been reported in several types of tumors (11,(13)(14)(15), and its expression levels have been correlated with clinical stages in breast cancer, renal cell carcinoma and prostate cancer; these reports further support that therapies targeting LDHA may provide useful strategies for controlling cancer progression. Moreover, previous reports using data from the Oncomine database showed that the mRNA levels of LDHA were up-regulated in GBM compared to those in matched normal tissues; these results prompted us to determine the correlation between LDHA expression levels and glioma malignancy (16).…”

Section: Discussionmentioning

confidence: 84%

“…In renal cell carcinoma, knocking down LDHA resulted in potential anticancer effects (14). Although the abnormal expression of LDHA has been reported in several cancers (10)(11)(12)(13)(14)(15), little is known about the expression pattern of LDHA and its underlying roles in GBM. Previous reports using data from the Oncomine database showed that the mRNA levels of LDHA were up-regulated in GBM compared to matched tissues (16); these finding prompted us to examine the underlying role of LDHA in glioma malignancy.…”

Section: Introductionmentioning

confidence: 99%

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Silencing LDHA inhibits proliferation, induces apoptosis and increases chemosensitivity to temozolomide in glioma cells

Zhang

Guo

et al. 2018

Oncol Lett

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Abstract. Glioblastoma multiforme (GBM) is a prevalent and aggressive disease, and the development of a novel therapy to better treat advanced GBM is urgently required. Lactate dehydrogenase A (LDHA), which functions as a key enzyme in transforming pyruvate into lactate, has attracted more attention in recent years due to its critical role in various types of advanced cancer. Previous data derived from the Oncomine database have shown that the expression of LDHA is higher in GBM tissues than that in corresponding normal control tissues. However, the association of LDHA levels with glioma clinical grades and the possible mechanisms of LDHA in GBM progression have not been investigated. The present study showed that there is a significant positive correlation between LDHA expression levels and tumor clinical stages. The knockdown of LDHA inhibited cell growth by inhibiting cell cycle progression and inducing apoptosis in glioma cell lines. Upon investigating the molecular mechanism, LDHA knockdown via siRNA treatment was associated with decreased cyclin D1 expression, increased cleavage of PARP, and altered B-cell lymphoma 2 and B-cell lymphoma 2-associated protein X expression. In addition, LDHA knockdown led to the marked downregulation of matrix metalloproteinase (MMP)-2, MMP-9, VE-Cadherin and vascular endothelial growth factor expression levels. Furthermore, knock down of LDHA enhanced the chemosensitivity of glioma cells to temozolomide (TMZ), a second-generation alkylating agent with activity against recurrent high-grade glioma. These findings support LDHA as a novel target for developing effective therapeutic strategies to treat GBM.

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Section: Discussionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Silencing LDHA inhibits proliferation, induces apoptosis and increases chemosensitivity to temozolomide in glioma cells

Zhang

Guo

et al. 2018

Oncol Lett

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“…Alpha-enolase (ENO1) promotes cell glycolysis, growth, migration, and invasion in non-small cell lung cancer through FAK-mediated PI3K/AKT pathway [15], and ENO1 is confirmed as a novel substrate of FBXW7 in colorectal cancer [16]. Lactate dehydrogenase A (LDHA) acts as oncogenic role in prostate cancer [17]. Aldolase A (ALDOA) may provide good survival prediction for stage I-IV colorectal cancer patients [18].…”

Section: Discussionmentioning

confidence: 99%

Aldolase B Overexpression is Associated with Poor Prognosis and Promotes Tumor Progression by Epithelial-Mesenchymal Transition in Colorectal Adenocarcinoma

Li¹,

Li²,

et al. 2017

Cell Physiol Biochem

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Background: Glycolysis is considered to be the root of cancer development and progression, which involved a multi-step enzymatic reaction. Our study aimed at figuring out which glycolysis enzyme participates in the development of colorectal cancer and its possible mechanisms. Methods: We firstly screened out Aldolase B (ALDOB) by performing qRT-PCR arrays of glycolysis-related genes in five paired liver metastasis and primary colorectal tissues, and further detected ALDOB protein with immunohistochemistry in tissue microarray (TMA) consisting of 229 samples from stage I-III colorectal cancer patients. CRISPR-Cas9 method was adopted to create knock out colon cancer cell lines (LoVo and SW480) of ALDOB. The effect of ALDOB on cell proliferation and metastasis was examined in vitro using colony formation assay as well as transwell migration and invasion assay, respectively. Results: In TMA, there was 64.6% of samples demonstrated strong intensity of ALDOB. High ALDOB expression were associated with poor overall survival and disease-free survival in both univariate and multivariate regression analyses (P<0.05). In vitro functional studies of CCK-8 demonstrated that silencing ALDOB expression significantly (P<0.05) inhibited proliferation, migration and invasion of colon cancer cells. Mechanically, silencing ALDOB activated epithelial markers and repressed mesenchymal markers, indicating inactivation of ALDOB may lead to inhibition of epithelial-mesenchymal transition (EMT). Conclusion: Upregulation of ALDOB promotes colorectal cancer metastasis by facilitating EMT and acts as a potential prognostic factor and therapeutic target in colorectal cancer.Q. Li and Y. Li contributed equally to this work.

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“…Lactate dehydrogenase A (LDHA) catalyzes the final step of glycolysis in which pyruvate is directly converted to lactate, indicating the critical role for maintaining glycolysis in tumorigenesis [14] . It has been reported that the expression of LDHA is abnormal in many human cancers, such as prostate cancer [15] , ovarian cancer [16] , pancreatic cancer [17,18] and breast cancer [19] . Meanwhile, inhibition of LDHA reduced several tumor progression [14][15][16][17] , indicating the underlying role of LDHA as a promising target for cancer therapy.…”

mentioning

confidence: 99%

“…It has been reported that the expression of LDHA is abnormal in many human cancers, such as prostate cancer [15] , ovarian cancer [16] , pancreatic cancer [17,18] and breast cancer [19] . Meanwhile, inhibition of LDHA reduced several tumor progression [14][15][16][17] , indicating the underlying role of LDHA as a promising target for cancer therapy. In breast cancer, silence of LDHA suppresses tumorigenicity through induction of oxidative stress-mediated mitochondrial pathway apoptosis [19] .…”

mentioning

confidence: 99%

Inhibition of LDHA Deliver Potential Anticancer Performance in Renal Cell Carcinoma

Wang

et al. 2016

Urol Int

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Purpose: Lactate dehydrogenase A (LDHA), which functions as a crucial enzyme in transforming from pyruvate into lactate, has been reported to be overexpressed in various advanced cancer and its silencing has turned out to be tumor suppressive. Previous studies have showed that the expression of LDHA was higher in renal cell carcinoma (RCC) than that in corresponding normal renal tissue. However, the function of LDHA in RCC, and its possible mechanism in tumor progression, has not been investigated. Methods: MTT and cell cycle assay were performed to explore the growth of the renal cells. Transwell assay for the migration and invasion and tube formation were conducted to detect the metastatic properties of the renal cancer. Results: Here, we show that siRNA-mediated knockdown of LDHA inhibits cell proliferation by decreasing cell cycle and promoting apoptosis in renal cancer cell lines. Mechanistically, LDHA siRNA treatment altered the expression of cell cycle- and apoptosis-related proteins, including p21, cyclin D1, Bcl-2 and Bax. In addition, LDHA siRNA treatment leads to markedly diminished migratory and invasive ability by reducing the expression of matrix metalloproteinase (MMP)-2 and MMP-9. Conclusions: These findings are consistent with the view that LDHA, as an oncogene, might be a potential therapeutic target in RCC.

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Inhibition of LDHA suppresses tumor progression in prostate cancer

Cited by 113 publications

References 18 publications

Silencing LDHA inhibits proliferation, induces apoptosis and increases chemosensitivity to temozolomide in glioma cells

Silencing LDHA inhibits proliferation, induces apoptosis and increases chemosensitivity to temozolomide in glioma cells

Aldolase B Overexpression is Associated with Poor Prognosis and Promotes Tumor Progression by Epithelial-Mesenchymal Transition in Colorectal Adenocarcinoma

Inhibition of LDHA Deliver Potential Anticancer Performance in Renal Cell Carcinoma

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