miR-1298 Inhibits Mutant KRAS-Driven Tumor Growth by Repressing FAK and LAMB3

Zhou, Ying; Dang, Jason; Chang, Kung-Yen; Yau, Edwin; Aza-Blanc, Pedro; Moscat, Jorge; Rana, Tariq M.

doi:10.1158/0008-5472.can-15-2936

Cited by 45 publications

(41 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These cell lines have previously been used by our lab to conduct a high-throughput screen of oncogenic KRAS synthetic lethal microRNAs (13). We transduced HCT116 WT and HCT116 MUT cells with the human GeCKO v2 library, which contains 65,383 sgRNA constructs targeting 19,050 human coding genes (3 sgRNAs per gene) and 1864 microRNAs (4 sgRNAs per gene) (8).…”

Section: Resultsmentioning

confidence: 99%

Genome-Wide CRISPR Screen for Essential Cell Growth Mediators in Mutant KRAS Colorectal Cancers

et al. 2017

Self Cite

View full text Add to dashboard Cite

Targeting mutant KRAS signaling pathways continues to attract attention as a therapeutic strategy for KRAS-driven tumors. In this study, we exploited the power of the CRISPR-Cas9 system to identify genes affecting the tumor xenograft growth of human mutant KRAS colorectal cancers (KRASMUT CRC). Using pooled lentiviral single guide RNA libraries, we conducted a genome-wide loss-of-function genetic screen in an isogenic pair of human CRC cell lines harboring mutant or wild-type KRAS. The screen identified novel and established synthetic enhancers or synthetic lethals for KRASMUT CRC, including targetable metabolic genes. Notably, genetic disruption or pharmacologic inhibition of the metabolic enzymes NAD kinase (NADK) or ketohexokinase (KHK) were growth inhibitory in vivo. Additionally, the chromatin remodeling protein INO80C was identified as a novel tumor suppressor in KRASMUT colorectal and pancreatic tumor xenografts. Our findings define a novel targetable set of therapeutic targets for KRASMUT tumors.

show abstract

Section: Resultsmentioning

confidence: 99%

Genome-Wide CRISPR Screen for Essential Cell Growth Mediators in Mutant KRAS Colorectal Cancers

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although this study provided a novel insight into the functional role of miR-1298 in NSCLC, the underlying mechanisms remain unclear. A study by Zhou et al indicated that miR-1298 could inhibit the mutation of KRAS, which serves as an oncogene in human malignancies, leading to the suppression in tumor growth [15]. In addition, Li et al demonstrated that miR-1298-5p exerted inhibiting effects on bladder cancer cell proliferation and invasion by downregulating connexin 43 [32].…”

Section: Discussionmentioning

confidence: 99%

“…A study by Xu et al analyzed the deregulated miR-NAs in NSCLC in silico, and microRNA-1298 (miR-1298) was found to be decreased in tumor cases compared with the normal controls [14]. Another study by Zhou et al indicates that miR-1298 is closely related with the KRAS mutation, which is determined as a key event during lung cancer progression [15]. However, the expression patterns of miR-1298 in NSCLC patients and its biological function are still unclear.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-1298 is downregulated in non-small cell lung cancer and suppresses tumor progression in tumor cells

Wang

et al. 2019

Diagn Pathol

View full text Add to dashboard Cite

Background: MicroRNAs (miRNAs) have been reported to serve pivotal roles in tumorigenesis. This study sough to assess the expression and clinical significance of microRNA-1298 (miR-1298) in patients with non-small cell lung cancer (NSCLC), and explore the functional role of miR-1298 in tumorigenesis. Methods: One hundred and twenty-one NSCLC patients were recruited in this study. The expression of miR-1298 was estimated using quantitative real-time PCR. Kaplan-Meier survival curves and Cox regression analysis were used to evaluate the prognostic value of miR-1298. Gain-and loss-of-function experiments were preformed to explore the biological function of miR-1298 in NSCLC cells. Results: Expression levels of miR-1298 were downregulated in NSCLC tissues and cells compared with the corresponding normal controls. The decreased expression of miR-1298 was associated with patients' lymph node metastasis and TNM stage. The low expression of miR-1298 predicted poor overall survival and served as an independent prognostic indicator in NSCLC patients. According to the cell experiments, NSCLC cell proliferation, migration and invasion were inhibited by the overexpression of miR-1298. Conclusion: All the data indicated that the downregulation of miR-1298 predicts poor prognosis of NSCLC, and the overexpression of miR-1298 in NSCLC cells leads to inhibited tumorigenesis. The aberrant miR-1298 may serve as a novel biomarker and therapeutic target in NSCLC.

show abstract

“…miR-1298 was identified in a global miRNA functional screen as selectively lethal to cells expressing mutated KRAS, which is an oncogene mutated in 20% of human cancers, mainly NSCLC and colorectal cancers. miR-1298 acts a tumor suppressor in KRAS-driven NSCLC and colorectal cancer cells by directly targeting the mRNA of both FAK and the Laminin subunit beta 3 (LAMB3), lowering their protein expression levels [153]. Interestingly, only expression of LAMB3, but not FAK, was upregulated by KRAS; yet silencing of either FAK or LAMB3 recapitulated miR-1298-induced cell-death in KRAS-dependent cancer cells.…”

Section: Non-coding Rnamentioning

confidence: 99%

Endogenous Control Mechanisms of FAK and PYK2 and Their Relevance to Cancer Development and Therapy

Naser¹,

Aldehaiman²,

Me³

et al. 2018

Preprint

View full text Add to dashboard Cite

Focal adhesion kinase (FAK) and its close paralogue, proline-rich tyrosine kinase 2 (PYK2), are key regulators of aggressive spreading and metastasis of cancer cells. While targeted small-molecule inhibitors of FAK and PYK2 are showing promising antitumor activity, their clinical long-term efficacy may be undermined by the strong capacity of cancer cells to evade anti-kinase drugs. In healthy cells, the expression and/or function of FAK and PYK2 is tightly controlled through modulation of gene expression, competing alternatively spliced forms, non-coding RNAs, and proteins that directly or indirectly affect kinase activation or protein stability. The molecular factors involved are frequently deregulated in cancer cells. Here, we review the endogenous mechanisms controlling FAK and PYK2, and discuss how these mechanisms could inspire or improve anticancer therapies.

show abstract

miR-1298 Inhibits Mutant KRAS-Driven Tumor Growth by Repressing FAK and LAMB3

Cited by 45 publications

References 39 publications

Genome-Wide CRISPR Screen for Essential Cell Growth Mediators in Mutant KRAS Colorectal Cancers

Genome-Wide CRISPR Screen for Essential Cell Growth Mediators in Mutant KRAS Colorectal Cancers

MicroRNA-1298 is downregulated in non-small cell lung cancer and suppresses tumor progression in tumor cells

Endogenous Control Mechanisms of FAK and PYK2 and Their Relevance to Cancer Development and Therapy

Contact Info

Product

Resources

About