MiR-21/RASA1 axis affects malignancy of colon cancer cells<i>via</i>RAS pathways

Gong, Bin; Liu, Wanwei; Nie, Wei; Li, Dongfeng; Xie, Zhenghui; Liu, Chao; Liu, Yan‐Hui; Mei, Ping; Li, Zijun

doi:10.3748/wjg.v21.i5.1488

Cited by 54 publications

(47 citation statements)

References 24 publications

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“…RASA1 in addition to its RasGAP activity has been speculated to be a RAS effector mediating the cellular effects of RAS through its interaction with p190RhoGAP and the subsequent inhibition of Rho activation (38). In agreement with the work reported here, in the colorectal cancer cell line RKO, decreased RASA1 expression mediated by miR-21 enhanced RAS signaling and invasion through transwells (42). …”

Section: Discussionsupporting

confidence: 91%

Transcriptional Regulation of miR-31 by Oncogenic KRAS Mediates Metastatic Phenotypes by Repressing RASA1

Kent

Mendell

Rottapel

2016

Molecular Cancer Research

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Activating KRAS mutations are nearly ubiquitous in pancreatic cancer occurring in more than 95% of clinical cases. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by binding sequences within the 3′UTRs of target mRNAs. An integral role for miRNAs in cancer pathogenesis is well established; however, the role of miRNAs in KRAS-mediated tumorigenesis is poorly characterized. Here it is demonstrated that expression of miR-31 is coupled to expression of oncogenic KRAS and activity of the MAPK pathway. MiR-31 is highly expressed in patient derived xenografts and a panel of pancreatic and colorectal cancer cells harboring activating KRAS mutations. The miR-31 host gene is a large non-coding RNA that correlates with miR-31 expression and enabled identification of the putative miR-31 promoter. Using luciferase reporters, a minimal RAS responsive miR-31 promoter was found to drive robust luciferase activity dependent on expression of mutant KRAS and the transcription factor ELK1. Furthermore, ELK1 interacts directly with the endogenous miR-31 promoter in a MAPK-dependent manner. Expression of enforced miR-31 significantly enhanced invasion and migration of multiple pancreatic cancer cells resulting from activation of RhoA through regulation of the miR-31 target gene RASA1. Importantly, acute knockdown of RASA1 phenocopied enforced miR-31 expression on the migratory behavior of pancreatic cancer cells through increased RhoA activation.

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Section: Discussionsupporting

confidence: 91%

Transcriptional Regulation of miR-31 by Oncogenic KRAS Mediates Metastatic Phenotypes by Repressing RASA1

Kent

Mendell

Rottapel

2016

Molecular Cancer Research

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“…Increasing number of studies suggested that miRNAs affect the progression, pathogenesis classification, diagnosis, and prognosis of cancer 8, 9, 10, 11.Recently, increased miRNAs have been implicated in the digestive diseases 12, 13, 14.Several studies have found that miR‐21, miR‐17, miR‐31, miR‐15, and others were critically involved in the pathogenesis of colorectal cancer 15, 16, 17, 18. miR‐17‐92 cluster consisted of six miRNAs (miR‐17, miR‐18a, miR‐19a, miR‐20a, miR‐19b, miR‐92a) and two paralogs (miR‐106b and miR‐106a).…”

Section: Introductionmentioning

confidence: 99%

A miRNAs panel promotes the proliferation and invasion of colorectal cancer cells by targeting GABBR1

et al. 2016

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MicroRNAs (miRNAs) have been implicated in the regulation of colorectal cancer. Despite the expression of miR‐17‐92 cluster in cancer has been gradually revealed, the role of each individual miRNAs in colorectal cancer still remains unclear. We studied the impact of miR‐106a/b, miR‐20a/b, and miR‐17 of miR‐17‐92 cluster on colorectal cancer cells. Real‐time quantitative polymerase chain reactions (RT‐PCR) were used to test these five miRNAs expression in colorectal cancer cell line HCT116. 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) assays, Bromodeoxyuridine (BrdU), and Transwell invasion assays were used to explore the effects of these five miRNAs in colorectal cancer cells. Luciferase reporter assay, RT‐PCR, and western blotting were performed to validate the interaction of these five miRNAs with the gamma‐amino‐butyric acid type B receptor 1(GABBR1). We found that these five miRNAs were significantly upregulated in colorectal cancer samples compared with normal tissues. Forced expression of these five miRNAs significantly promoted HCT116 and HT‐29 cells proliferation and invasion. We further found that these five miRNAs function as oncogenes in colorectal cancer by specifically binding to the 3‐untranslated regions (3′UTR) of GABBR1.Furthermore, inhibition of GABBR1 could mimic the function of miRNAs in HCT116 cells, while overexpression of GABBR1 blocked the function of miRNAs‐promoted proliferation and invasion. In conclusion, miR‐106a/b, miR‐20a/b, and miR‐17 contribute to the proliferation and invasion of colorectal cancer by targeting their common target gene, GABBR1, and played a critical role in the proliferation and invasion of colorectal cancer.

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“…8 RASA1 contributed to miR-335Yinduced tumor cell invasion and migration in gastric cancer 9 and promoted miR-21Ymediated malignancy in colon cancer cells. 10 However, the exact role of RASA1 in the cervical cancer remains to be understood, so we next focused on how miR-21/RASA1 played a role in lymph node metastasis in cervical cancer.…”

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confidence: 99%

Circulating MicroRNA-21 Is Involved in Lymph Node Metastasis in Cervical Cancer by Targeting RASA1

Zhang¹,

Zhan²,

Yan³

et al. 2016

International Journal of Gynecological Cancer

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The aims of this study were to discover if increased circulating microRNA-21 (miR-21) expression in serum is associated with lymph node metastasis in patients with cervical cancer and look further into the molecular mechanism of these. Whole-blood samples from 89 patients who have been histopathologically confirmed as having cervical cancer and 20 control subjects were collected, and then the association between lymph node metastasis and the level of circulating miR-21 was compared. Then cervical cancer cell lines HeLa (HPV-18 DNA, E6/E7RNA) and HT-3 (HPV DNA, E6/E7RNA) were used to confirm the interaction between miR-21 and RASA1. The role of RASA1 in cervical cancer cell migration was also studied in HeLa. Increased circulating miR-21 expression in serum is associated with lymph node metastasis in patients with cervical cancer. MicroRNA-21 reduces RASA1 expression in cervical cancer cell lines and promotes cervical cancer cell migration via RASA1. Furthermore, Ras-induced epithelial-mesenchymal transition contributes to miR-21/RASA1 axis promoting cervical cancer cell migration. Circulating miR-21 in serum could be a promising biomarker in auxiliary diagnosis of lymph node metastasis in cervical cancer, and inhibition of miR-21/RASA1 axis could be a possible strategy to restrain migration of cervical cancer.

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MiR-21/RASA1 axis affects malignancy of colon cancer cellsviaRAS pathways

Abstract: RASA1 is a target gene of miR-21, which promotes malignant behaviors of RKO cells through regulation of RASA1 expression.

Cited by 54 publications

References 24 publications

Transcriptional Regulation of miR-31 by Oncogenic KRAS Mediates Metastatic Phenotypes by Repressing RASA1

Transcriptional Regulation of miR-31 by Oncogenic KRAS Mediates Metastatic Phenotypes by Repressing RASA1

A miRNAs panel promotes the proliferation and invasion of colorectal cancer cells by targeting GABBR1

Circulating MicroRNA-21 Is Involved in Lymph Node Metastasis in Cervical Cancer by Targeting RASA1

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