MicroRNA-145 targets MUC13 and suppresses growth and invasion of pancreatic cancer

Sheema Khan, Mara C. Ebeling, Mohd S. Zaman, Mohammed Sikander, Murali Yallapu, Neeraj Chauhan, Ashley M. Yacoubian, Stephen W. Behrman, Nadeem Zafar, Deepak Kumar, Paul A. Thompson, Meena Jaggi, Subhash Chauhan

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Pancreatic cancer has a poor prognosis due to late diagnosis and ineffective therapeutic multimodality. MUC13, a transmembrane mucin is highly involved in pancreatic cancer progression. Thus, understanding its regulatory molecular mechanisms may offer new avenue of therapy for prevention/treatment of pancreatic cancer. Herein, we report a novel microRNA (miR-145)-mediated mechanism regulating aberrant MUC13 expression in pancreatic cancer. We report that miR-145 expression inversely correlates with MUC13 expression in pancreatic cancer cells and human tumor tissues. miR-145 is predominantly present in normal pancreatic tissues and early Pancreatic Ductal Adenocarcinoma (PDAC) precursor lesions (PanIN I) and is progressively suppressed over the course of development from PanIN II/III to late stage poorly differentiated PDAC. We demonstrate that miR-145 targets 3' untranslated region of MUC13 and thus downregulates MUC13 protein expression in cells. Interestingly, transfection of miR-145 inhibits cell proliferation, invasion and enhances gemcitabine sensitivity. It causes reduction of HER2, P-AKT, PAK1 and an increase in p53. Similar results were found when MUC13 was specifically inhibited by shRNA directed at MUC13. Additionally, intratumoral injections of miR-145 in xenograft mice inhibited tumor growth via suppression of MUC13 and its downstream target, HER2. These results suggest miR-145 as a novel regulator of MUC13 in pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)7599-7609
Number of pages11
JournalOncotarget
Volume5
Issue number17
DOIs
StatePublished - Jan 1 2014

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MicroRNAs
Pancreatic Neoplasms
Growth
gemcitabine
Adenocarcinoma
Delayed Diagnosis
3' Untranslated Regions
Mucins
Heterografts
Small Interfering RNA
Transfection
Neoplasms
Therapeutics
Down-Regulation
Cell Proliferation
Injections
Proteins

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

MicroRNA-145 targets MUC13 and suppresses growth and invasion of pancreatic cancer. / Khan, Sheema; Ebeling, Mara C.; Zaman, Mohd S.; Sikander, Mohammed; Yallapu, Murali; Chauhan, Neeraj; Yacoubian, Ashley M.; Behrman, Stephen W.; Zafar, Nadeem; Kumar, Deepak; Thompson, Paul A.; Jaggi, Meena; Chauhan, Subhash.

In: Oncotarget, Vol. 5, No. 17, 01.01.2014, p. 7599-7609.

Research output: Contribution to journalArticle

Khan, S, Ebeling, MC, Zaman, MS, Sikander, M, Yallapu, M, Chauhan, N, Yacoubian, AM, Behrman, SW, Zafar, N, Kumar, D, Thompson, PA, Jaggi, M & Chauhan, S 2014, 'MicroRNA-145 targets MUC13 and suppresses growth and invasion of pancreatic cancer', Oncotarget, vol. 5, no. 17, pp. 7599-7609. https://doi.org/10.18632/oncotarget.2281
Khan, Sheema ; Ebeling, Mara C. ; Zaman, Mohd S. ; Sikander, Mohammed ; Yallapu, Murali ; Chauhan, Neeraj ; Yacoubian, Ashley M. ; Behrman, Stephen W. ; Zafar, Nadeem ; Kumar, Deepak ; Thompson, Paul A. ; Jaggi, Meena ; Chauhan, Subhash. / MicroRNA-145 targets MUC13 and suppresses growth and invasion of pancreatic cancer. In: Oncotarget. 2014 ; Vol. 5, No. 17. pp. 7599-7609.
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