Growth-arrest-specific 7C protein inhibits tumor metastasis via the N-WASP/FAK/F-actin and hnRNP U/β-TrCP/β-catenin pathways in lung cancer

Tseng, Ruo Chia; Chang, Jui-Chi; Mao, Jiou Shan; Tsai, Charng Dar; Wu, Pei Chen; Lin, Cuei Jyuan; Lu, Yi; Liao, Shengyou; Cheng, Hsiu Chi; Hsu, Han Shui; Wang, Yi‐Ching

doi:10.18632/oncotarget.6229

Cited by 21 publications

(19 citation statements)

References 36 publications

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“…Previous studies report the function of hnRNP U as an mRNA stabilizer . Also, some works prove that hnRNP U exerts suppressive effect on NSCLC progression . Therefore, we speculated that LIMD1‐AS1 regulated LIMD1 mRNA stability through hnRNP U.…”

Section: Resultsmentioning

confidence: 87%

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LIMD1‐AS1 suppressed non‐small cell lung cancer progression through stabilizing LIMD1 mRNA via hnRNP U

et al. 2020

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Background Non‐small cell lung cancer (NSCLC) occupies the majority of lung cancer cases and is notorious for the awful prognosis. LIM domains‐containing 1 (LIMD1) is suggested as a tumor suppressor in lung cancer, but its mechanism in NSCLC remains elusive. Present study aimed to uncover the mechanism of LIMD1 in NSCLC. Methods qRT‐PCR was performed to analyze the level of LIMD1. The functions of LIMD1 in NSCLC cells were evaluated by CCK‐8, EdU, and caspase‐3 activity assays. RIP and pull‐down assays were applied to determine the interaction of LIMD1 with heterogeneous nuclear ribonucleoprotein U (hnRNP U) and LIMD1‐AS1. Results LIMD1 was downregulated in NSCLC samples and cells. Functionally, LIMD1 hindered proliferation and drove apoptosis in NSCLC cells. Moreover, long noncoding RNA (lncRNA) LIMD1 antisense RNA 1 (LIMD1‐AS1) was downregulated in NSCLC samples and cell lines. LIMD1‐AS1 knockdown abrogated NSCLC cell growth in vitro and in vivo. Mechanistically, LIMD1‐AS1 stabilized LIMD1 mRNA through interacting with hnRNP U. Rescue experiments suggested that LIMD1‐AS1 repressed NSCLC progression through LIMD1. Conclusions LIMD1‐AS1 suppressed NSCLC progression through stabilizing LIMD1 mRNA via hnRNP U, providing new thoughts for the improvement of molecular‐targeted therapy for NSCLC.

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Section: Resultsmentioning

confidence: 87%

“…Recent reports show the implication of hnRNP U in modulating DNA damage response and cell apoptosis . In lung cancer, hnRNP U is reported to be downregulated, and reduces β‐catenin expression by β‐TrCP to inhibit lung cancer progression . Notably, hnRNP U is a regulator of mRNA stability .…”

Section: Introductionmentioning

confidence: 99%

LIMD1‐AS1 suppressed non‐small cell lung cancer progression through stabilizing LIMD1 mRNA via hnRNP U

et al. 2020

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“…On the contrary, GAS7 has a proproliferative role in pre-B acute lymphoblastic leukemia cells, possibly through regulating Stat5, AKT, and Erk proliferation signals [35,36]. GAS7 is also well known for its regulatory effect on actin cytoskeleton reorganization [37]. Interestingly, Reshetnikova et al [38] pointed out that actin cytoskeleton-dependent G0/G1 cell cycle arrest may be associated with the CDK/cyclin pathway.…”

Section: Discussionmentioning

confidence: 99%

miR-362-5p promotes cell proliferation and cell cycle progression by targeting GAS7 in acute myeloid leukemia

Chen

et al. 2020

Human Cell

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Recently, miR-362-5p has attracted special interest as a novel prognostic predictor in acute myeloid leukemia (AML). However, its biological function and underlying molecular mechanism in AML remain to be further defined. Herein, we found that a significant increase in miR-362-5p expression was observed in AML patients and cell lines using quantitative realtime PCR. The expression of miR-362-5p was altered in THP-1 and HL-60 cells by transfecting with miR-362-5p mimic or inhibitor. A series of experiments showed that inhibition of miR-362-5p expression significantly suppressed cell proliferation, induced G0/G1 phase arrest and attenuated tumor growth in vivo. On the contrary, ectopic expression of miR-362-5p resulted in enhanced cell proliferation, cell cycle progression and tumor growth. Moreover, growth arrest-specific 7 (GAS7) was confirmed as a direct target gene of miR-362-5p and was negatively modulated by miR-362-5p. GAS7 overexpression imitated the tumor suppressive effect of silenced miR-362-5p on THP-1 cells. Furthermore, miR-362-5p knockdown or GAS7 overexpression obviously down-regulated the expression levels of PCNA, CDK4 and cyclin D1, but up-regulated p21 expression. Collectively, our findings demonstrate that miR-362-5p exerts oncogenic effects in AML by directly targeting GAS7, which might provide a promising therapeutic target for AML.

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“…For example, epigenetic silencing of ADAMTS19 is commonly involved in colorectal and mucinous ovarian cancer (3). GAS7C, a metastasis suppressor, was found to be hypermethylated in its promoter region in lung cancer (4). Hypomethylation of the ELMO3 promoter induced upregulation of its mRNA and ultimately resulted in the metastasis of lung cancer (5).…”

Section: Introductionmentioning

confidence: 99%

Epigenetic activation of WHSC1 functions as an oncogene and is associated with poor prognosis in cervical cancer

Sun

2017

Oncology Reports

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Overexpression of Wolf-Hirschhorn syndrome candidate 1 (WHSC1) is commonly observed in various types of tumors. However, the potential mechanism responsible for this molecular event is poorly understood. In the present study, we found that the mRNA levels of WHSC1 were significantly increased in cervical cancer cells, and that CpG sites were almost fully methylated in HaCaT cells, but partially methylated in HeLa and C33A cells. Clinically, the results of quantitative methylation-specific PCR (QMSP) and quantitative real-time PCR (qRT-PCR), showed that methylation levels of the WHSC1 gene were significantly decreased in cervical cancer tumors and inversely correlated with its mRNA expression levels. Both decreased methylation of WHSC1 and increased mRNA were associated with cancer progression and poor prognosis. In addition, overexpression of WHSC1 contributed to cell proliferation, migration and invasion, while cells with WHSC1 knockdown exhibited the opposite effects. AKT/metalloproteinase-2 (MMP-2) signaling was activated and inactivated upon overexpression and silencing of WHSC1, respectively. Silencing of WHSC1 also suppressed tumor growth in a xenograft model. In conclusion, WHSC1 is hypomethylated in cervical cancer, and consequent overexpression of WHSC1 mRNA may promote cervical carcinogenesis by activating the AKT/MMP-2 signaling pathway.

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Growth-arrest-specific 7C protein inhibits tumor metastasis via the N-WASP/FAK/F-actin and hnRNP U/β-TrCP/β-catenin pathways in lung cancer

Cited by 21 publications

References 36 publications

LIMD1‐AS1 suppressed non‐small cell lung cancer progression through stabilizing LIMD1 mRNA via hnRNP U

LIMD1‐AS1 suppressed non‐small cell lung cancer progression through stabilizing LIMD1 mRNA via hnRNP U

miR-362-5p promotes cell proliferation and cell cycle progression by targeting GAS7 in acute myeloid leukemia

Epigenetic activation of WHSC1 functions as an oncogene and is associated with poor prognosis in cervical cancer

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