Deregulation of the miR-16-KRAS axis promotes colorectal cancer

You, Chun‐Xiang; Liang, Hongwei; Sun, Wei; Li, Jialu; Liu, Yanqing; Fan, Qian; Zhang, Haiyang; Yue, Xin; Li, Jing; Chen, Xi; Ba, Yi

doi:10.1038/srep37459

Cited by 32 publications

(25 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…H19 long non-coding RNA (lncRNA) blocks K-Ras mRNA degradation by antagonizing Let-7 miRNAs. 9 Moreover, miR-16 directly targets the 3′-UTR of KRAS mRNA to block K-Ras expression 10 ( Figure 1 ). The extent to which miRNAs cross react with mRNAs of other ras oncogenes is not well understood.…”

Section: K-ras: Genetic Regulation Of Expression and Activationmentioning

confidence: 99%

Molecular genetics and cellular events of K-Ras-driven tumorigenesis

et al. 2017

View full text Add to dashboard Cite

Cellular transformation and the accumulation of genomic instability are the two key events required for tumorigenesis. K-Ras (Kirsten-rat sarcoma viral oncogene homolog) is a prominent oncogene that has been proven to drive tumorigenesis. K-Ras also modulates numerous genetic regulatory mechanisms and forms a large tumorigenesis network. In this review, we track the genetic aspects of K-Ras signaling networks and assemble the sequence of cellular events that constitute the tumorigenesis process, such as regulation of K-Ras expression (which is influenced by miRNA, small nucleolar RNA and lncRNA), activation of K-Ras (mutations), generation of reactive oxygen species (ROS), induction of DNA damage and apoptosis, induction of DNA damage repair pathways and ROS detoxification systems, cellular transformation after apoptosis by the blebbishield emergency program and the accumulation of genomic/chromosomal instability that leads to tumorigenesis.

show abstract

Section: K-ras: Genetic Regulation Of Expression and Activationmentioning

confidence: 99%

Molecular genetics and cellular events of K-Ras-driven tumorigenesis

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Finally, an ideal HK miRNA to be used in CRC studies should not be involved in cancer biology. However, for the widely used HK miRNA miR-16-5p there are lots of reports demonstrating its deregulation and implication in cancer processes, including CRC, regulating onco/tumor suppressor genes and having an important role in cell growth in cancer [34][35][36]. By contrast, no relation with colon cancer processes has been found for miR-1228-3p that has been only related with the regulation of some metabolic pathways and organ morphology [19].…”

Section: Discussionmentioning

confidence: 99%

Validation of miR-1228-3p as Housekeeping for MicroRNA Analysis in Liquid Biopsies from Colorectal Cancer Patients

et al. 2019

View full text Add to dashboard Cite

Background: Circulating microRNA (miRNA) analysis is a growing research field. However, it usually requires an endogenous control or housekeeping (HK) in order to normalize expression of specific miRNAs throughout different samples. Unfortunately, no adequate HK for circulating miRNA analysis is still known in the colorectal cancer (CRC) context whereas several have been suggested. Hence, our aims were to validate the previously suggested miR-1228-3p as HK for CRC studies, to compare its suitability with the widely used miR-16-5p, and to evaluate the influence of hemolysis on both miRNAs. Methods: We analyzed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) the expression of miR-1228-3p, miR-16-5p and the spike-in cel-miR-39 in a set of 297 plasmas (92 CRC, 101 advanced adenomas -AA-, and 100 controls) and 213 serum samples (59 CRC, 74 AA and 80 controls). We also analyzed both miRNAs depending on the hemolysis degree in 7 plasmas and 31 serums. Results: Levels of miR-1228-3p and miR-16-5p did not show significant differences between groups although miR-16-5p exhibited more variability in plasma and serum samples. Importantly, the combination of cel-miR-39 and miR-1228-3p was the most stable one. Moreover, we observed that miR-16-5p was significantly influenced by hemolysis in contrast with miR-1228-3p that exhibited no correlation with this confounding factor in both biofluids. Conclusion: MiR-1228-3p has been validated as an adequate endogenous control for circulating miRNA analysis in CRC and AA liquid biopsies.

show abstract

“…In pancreatic adenocarcinoma, miR-206 modulated cell proliferation, invasion and lymphangiogenesis in through targeting of several genes including KRAS [42]. Multiple studies have also implicated that KRAS may also be regulated by a number of miRNAs, including miR-16 and -337 in colorectal cancer [43,44], miR-216b in nasopharyngeal carcinoma [45], and miR-30c and -21 in non-small-cell lung cancer, and -134 in breast cancer cells [46]. However, to the best of our knowledge, this is the first study to correlate the expression of KRAS with the modulatory effect of miR-206 in TNBC.…”

Section: Discussionmentioning

confidence: 99%

VEGF and KRAS are Potential Targets of miR-206 Modulation in Triple Negative Breast Cancer

Feky¹,

Ibrahim²,

Nassar³

et al. 2019

JCRT

View full text Add to dashboard Cite

Triple negative is a subtype of breast cancer characterized by lack of expression of hormone receptors (ER, PR and Her2/neu). Due to the limited treatment options, the search for novel treatment targets continues. The aim of this study was to assess the differential expression of miR-206, VEGF and KRAS in TNBC and non-TNBC tissues and cell lines and to evaluate the modulatory effect of miR-206 on the key oncogenic targets VEGF and KRAS. The expression of miR-206, VEGF and KRAS was quantified using real time PCR in both paraffin embedded breast cancer and adjacent tissues as well as in MDA-MB-231 and MCF-7 cell lines. Cell lines were transfected with different concentrations of miR-206 mimic and their viability were assessed using MTT assay. Our results indicated that miR-206 was significantly downregulated in cancerous compared to non-cancerous tissues with a more pronounced downregulation in TNBC than non-TNBC tissues. VEGF and KRAS were significantly upregulated in TNBC compared to non-TNBC and their expression was negatively correlated to miR-206 expression. Transfection of TNBC and non-TNBC cell lines with miR-206 mimic resulted in a dose dependent reduction in cell viability as well as a significant reduction in VEGF and KRAS expression. In conclusion, based on our combined human tissues and cell line-based investigations we can suggest that VEGF and KRAS may be potential targets for miR-206-mediated regulation and that their targeting by miR-206 can be a highly efficient therapeutic strategy in TNBC.

show abstract

Deregulation of the miR-16-KRAS axis promotes colorectal cancer

Cited by 32 publications

References 43 publications

Molecular genetics and cellular events of K-Ras-driven tumorigenesis

Molecular genetics and cellular events of K-Ras-driven tumorigenesis

Validation of miR-1228-3p as Housekeeping for MicroRNA Analysis in Liquid Biopsies from Colorectal Cancer Patients

VEGF and KRAS are Potential Targets of miR-206 Modulation in Triple Negative Breast Cancer

Contact Info

Product

Resources

About