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Open Access 01-12-2014 | Research highlight

MicroRNA-mediated regulation of KRAS in cancer

Authors: Minlee Kim, Frank J Slack

Published in: Journal of Hematology & Oncology | Issue 1/2014

Abstract

While microRNAs (miRNAs) and the KRAS oncogene are known to be dysregulated in various cancers, little is known about the role of miRNAs in the regulation of KRAS in cancer. Here we review a selection of studies published in 2014 that have contributed to our understanding of the molecular mechanisms of KRAS regulation by miRNAs and the clinical relevance of sequence variants that may interfere with functional miRNA-mediated KRAS regulation.

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Yu S, Lu Z, Liu C, Meng Y, Ma Y, Zhao W, Liu J, Yu J, Chen J: miRNA-96 suppresses KRAS and functions as a tumor suppressor gene in pancreatic cancer. Cancer Res. 2010, 70: 6015-6025. 10.1158/0008-5472.CAN-09-4531.CrossRefPubMed

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Liao W-T, Ye Y-P, Zhang N-J, Li T-T, Wang S-Y, Cui Y-M, Qi L, Wu P, Jiao H-L, Xie Y-J, Zhang C, Wang J-X, Ding Y-Q: MicroRNA-30b functions as a tumour suppressor in human colorectal cancer by targeting KRAS, PIK3CD and BCL2. J Pathol. 2014, 232: 415-427. 10.1002/path.4309.CrossRefPubMed

10.

Tanaka M, Suzuki HI, Shibahara J, Kunita A, Isagawa T, Yoshimi A, Kurokawa M, Miyazono K, Aburatani H, Ishikawa S, Fukayama M: EVI1 oncogene promotes KRAS pathway through suppression of microRNA-96 in pancreatic carcinogenesis. Oncogene. 2014, 33: 2454-2463. 10.1038/onc.2013.204.CrossRefPubMed

11.

Zhang Y, Kim J, Mueller AC, Dey B, Yang Y, Lee D-H, Hachmann J, Finderle S, Park DM, Christensen J, Schiff D, Purow B, Dutta A, Abounader R: Multiple receptor tyrosine kinases converge on microRNA-134 to control KRAS, STAT5B, and glioblastoma. Cell Death Differ. 2014, 21: 720-734. 10.1038/cdd.2013.196.PubMedCentralCrossRefPubMed

12.

Chin LJ, Ratner E, Leng S, Zhai R, Nallur S, Babar I, Muller R-U, Straka E, Su L, Burki EA, Crowell RE, Patel R, Kulkarni T, Homer R, Zelterman D, Kidd KK, Zhu Y, Christiani DC, Belinsky SA, Slack FJ, Weidhaas JB: A SNP in a let-7 microRNA complementary site in the KRAS 3’ untranslated region increases non-small cell lung cancer risk. Cancer Res. 2008, 68: 8535-8540. 10.1158/0008-5472.CAN-08-2129.PubMedCentralCrossRefPubMed

13.

Cerne J-Z, Stegel V, Gersak K, Novakovic S: KRAS rs61764370 is associated with HER2-overexpressed and poorly-differentiated breast cancer in hormone replacement therapy users: a case control study. BMC Cancer. 2012, 12: 105-10.1186/1471-2407-12-105.PubMedCentralCrossRefPubMed

14.

Paranjape T, Heneghan H, Lindner R, Keane FK, Hoffman A, Hollestelle A, Dorairaj J, Geyda K, Pelletier C, Nallur S, Martens JW, Hooning MJ, Kerin M, Zelterman D, Zhu Y, Tuck D, Harris L, Miller N, Slack F, Weidhaas J: A 3′-untranslated region KRAS variant and triple-negative breast cancer: a case-control and genetic analysis. Lancet Oncol. 2011, 12: 377-386. 10.1016/S1470-2045(11)70044-4.PubMedCentralCrossRefPubMed

15.

Ratner E, Lu L, Boeke M, Barnett R, Nallur S, Chin LJ, Pelletier C, Blitzblau R, Tassi R, Paranjape T, Hui P, Godwin AK, Yu H, Risch H, Rutherford T, Schwartz P, Santin A, Matloff E, Zelterman D, Slack FJ, Weidhaas JB: A KRAS-variant in ovarian cancer acts as a genetic marker of cancer risk. Cancer Res. 2010, 70: 6509-6515. 10.1158/0008-5472.CAN-10-0689.PubMedCentralCrossRefPubMed

16.

Ratner ES, Keane FK, Lindner R, Tassi RA, Paranjape T, Glasgow M, Nallur S, Deng Y, Lu L, Steele L, Sand S, Muller R-U, Bignotti E, Bellone S, Boeke M, Yao X, Pecorelli S, Ravaggi A, Katsaros D, Zelterman D, Cristea MC, Yu H, Rutherford TJ, Weitzel JN, Neuhausen SL, Schwartz PE, Slack FJ, Santin AD, Weidhaas JB: A KRAS variant is a biomarker of poor outcome, platinum chemotherapy resistance and a potential target for therapy in ovarian cancer. Oncogene. 2011, 30: 1542-1550. 10.1038/onc.2010.536.CrossRef

17.

Grechukhina O, Petracco R, Popkhadze S, Massasa E, Paranjape T, Chan E, Flores I, Weidhaas JB, Taylor HS: A polymorphism in a let-7 microRNA binding site of KRAS in women with endometriosis. EMBO Mol Med. 2012, 4: 206-217. 10.1002/emmm.201100200.PubMedCentralCrossRefPubMed

18.

Zhang W, Winder T, Ning Y, Pohl A, Yang D, Kahn M, Lurje G, LaBonte MJ, Wilson PM, Gordon MA, Hu-Lieskovan S, Mauro DJ, Langer C, Rowinsky EK, Lenz HJ: A let-7 microRNA-binding site polymorphism in 3′-untranslated region of KRAS gene predicts response in wild-type KRAS patients with metastatic colorectal cancer treated with cetuximab monotherapy. Ann Oncol. 2011, 22: 104-109. 10.1093/annonc/mdq315.CrossRefPubMed

19.

Sebio A, Paré L, Páez D, Salazar J, González A, Sala N, del Río E, Martín-Richard M, Tobeña M, Barnadas A, Baiget M: The LCS6 polymorphism in the binding site of let-7 microRNA to the KRAS 3′-untranslated region: its role in the efficacy of anti-EGFR-based therapy in metastatic colorectal cancer patients. Pharmacogenet Genomics. 2013, 23: 142-147. 10.1097/FPC.0b013e32835d9b0b.CrossRefPubMed

20.

Nelson HH, Christensen BC, Plaza SL, Wiencke JK, Marsit CJ, Kelsey KT: KRAS mutation, KRAS-LCS6 polymorphism, and non-small cell lung cancer. Lung Cancer. 2010, 69: 51-53. 10.1016/j.lungcan.2009.09.008.PubMedCentralCrossRefPubMed

21.

Pharoah PDP, Palmieri RT, Ramus SJ, Gayther SA, Andrulis IL, Anton-Culver H, Antonenkova N, Antoniou AC, Goldgar D, Beattie MS, Beckmann MW, Birrer MJ, Bogdanova N, Bolton KL, Brewster W, Brooks-Wilson A, Brown R, Butzow R, Caldes T, Caligo MA, Campbell I, Chang-Claude J, Chen YA, Cook LS, Couch FJ, Cramer DW, Cunningham JM, Despierre E, Doherty JA, Dörk T: The role of KRAS rs61764370 in invasive epithelial ovarian cancer: implications for clinical testing. Clin Cancer Res. 2011, 17: 3742-3750. 10.1158/1078-0432.CCR-10-3405.PubMedCentralCrossRefPubMed

22.

Kjersem JB, Ikdahl T, Guren T, Skovlund E, Sorbye H, Hamfjord J, Pfeiffer P, Glimelius B, Kersten C, Solvang H, Tveit KM, Kure EH: Let-7 miRNA-binding site polymorphism in the KRAS 3′UTR; colorectal cancer screening population prevalence and influence on clinical outcome in patients with metastatic colorectal cancer treated with 5-fluorouracil and oxaliplatin +/- cetuximab. BMC Cancer. 2012, 12: 534-10.1186/1471-2407-12-534.PubMedCentralCrossRefPubMed

23.

Sha D, Lee AM, Shi Q, Alberts SR, Sargent DJ, Sinicrope FA, Diasio RB: Association study of the let-7 miRNA-complementary site variant in the 3′ untranslated region of the KRAS gene in stage III colon cancer (NCCTG N0147 Clinical Trial). Clin Cancer Res. 2014, 20: 3319-3327. 10.1158/1078-0432.CCR-14-0069.PubMedCentralCrossRefPubMed

24.

Lee LJ, Ratner E, Uduman M, Winter K, Boeke M, Greven KM, King S, Burke TW, Underhill K, Kim H, Boulware RJ, Yu H, Parkash V, Lu L, Gaffney D, Dicker AP, Weidhaas J: The KRAS-Variant and miRNA Expression in RTOG Endometrial Cancer Clinical Trials 9708 and 9905. PLoS One. 2014, 9: e94167-10.1371/journal.pone.0094167.PubMedCentralCrossRefPubMed

25.

Wang W-Y, Chien Y-C, Wong Y-K, Lin Y-L, Lin J-C: Effects of KRAS mutation and polymorphism on the risk and prognosis of oral squamous cell carcinoma. Head Neck. 2012, 34: 663-666. 10.1002/hed.21792.CrossRefPubMed

26.

Li Z-H, Pan X-M, Han B-W, Guo X-M, Zhang Z, Jia J, Gao L-B: A let-7 binding site polymorphism rs712 in the KRAS 3′ UTR is associated with an increased risk of gastric cancer. Tumour Biol. 2013, 34: 3159-3163. 10.1007/s13277-013-0885-x.CrossRefPubMed

27.

Pan X-M, Sun R-F, Li Z-H, Guo X-M, Zhang Z, Qin H-J, Xu G-H, Gao L-B: A let-7 KRAS rs712 polymorphism increases colorectal cancer risk. Tumour Biol. 2014, 35: 831-835. 10.1007/s13277-013-1114-3.CrossRefPubMed

28.

Jin H, Liang Y, Wang X, Zhu J, Sun R, Chen P, Nie X, Gao L, Zhang L: Association between a functional polymorphism rs712 within let-7-binding site and risk of papillary thyroid cancer. Med Oncol. 2014, 31: 221-10.1007/s12032-014-0221-3.CrossRefPubMed

29.

Kim M, Chen X, Chin LJ, Paranjape T, Speed WC, Kidd KK, Zhao H, Weidhaas JB, Slack FJ: Extensive sequence variation in the 3′ untranslated region of the KRAS gene in lung and ovarian cancer cases. Cell Cycle. 2014, 13: 1030-1040. 10.4161/cc.27941.PubMedCentralCrossRefPubMed

30.

Sabarinathan R, Wenzel A, Novotny P, Tang X, Kalari KR, Gorodkin J: Transcriptome-wide analysis of UTRs in non-small cell lung cancer reveals cancer-related genes with SNV-induced changes on RNA secondary structure and miRNA target sites. PLoS One. 2014, 9: e82699-10.1371/journal.pone.0082699.PubMedCentralCrossRefPubMed

Title: MicroRNA-mediated regulation of KRAS in cancer
Authors: Minlee Kim
Frank J Slack
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Journal of Hematology & Oncology / Issue 1/2014
Electronic ISSN: 1756-8722
DOI: https://doi.org/10.1186/s13045-014-0084-2

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