miR-30a-5p enhances paclitaxel sensitivity in non-small cell lung cancer through targeting BCL-2 expression.

J Mol Med (Berl) 2017 08 9;95(8):861-871. Epub 2017 May 9.

Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, China.

Lung cancer remains the leading cause of cancer-related death worldwide. Paclitaxel, either as monotherapy or combined with other agents, is the standard treatment for advanced non-small cell lung cancer (NSCLC), the most common type of lung cancer. However, both de novo and acquired resistance against paclitaxel frequently occurs and represents a huge clinical problem. The underlying mechanisms remain poorly characterized. Here, by comparing microRNA (miRNA) expression levels using miRNA arrays, we observed differential expression of miR-30a-5p in two independent lung cancer cell pairs (paclitaxel-resistant vs paclitaxel-sensitive A549 cell lines). Overexpression of miR-30a-5p sensitizes NSCLC cells to paclitaxel both in vitro and in vivo. In addition, miR-30a-5p increases paclitaxel sensitivity by promoting chemotherapy-induced apoptosis via downregulating BCL-2, a key apoptosis regulator. High miR-30a-5p expression is positively correlated with enhanced responsiveness to paclitaxel and predicts a more favorable clinical outcome in NSCLC patients. Moreover, miR-30a-5p expression is negatively correlated with BCL-2 expression in NSCLC tissues. These data indicate that miR-30a-5p may be useful to treat paclitaxel-resistant lung cancer and may also provide a biomarker to predict paclitaxel responsiveness in lung cancer.

Key Messages: BCL-2 is a novel direct target of miR-30a-5p. miR-30a-5p enhances NSCLC paclitaxel sensitivity in vitro and in vivo. miR-30a-5p sensitizes NSCLC cells to paclitaxel by inducing apoptosis through BCL-2 inhibition. miR-30a-5p negatively correlates with BCL-2 and predicts a favorable clinical outcome in NSCLC patients.

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http://dx.doi.org/10.1007/s00109-017-1539-zDOI Listing
August 2017
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References

(Supplied by CrossRef)

A Jemal et al.
CA Cancer J Clin 2011

R Siegel et al.
CA Cancer J Clin 2014

AY Chang et al.
J Natl Cancer Inst 1993

WK Murphy et al.
J Natl Cancer Inst 1993

H Zheng et al.
Oncotarget 2014

JR Vargas et al.
Mol Pharm 2014

A Goncalves et al.
Proc Natl Acad Sci U S A 2001

W He et al.
Med Oncol 2014

M Kavallaris et al.
Nat Rev Cancer 2010

CK Ingemarsdotter et al.
Mol Oncol 2015

JH Choi et al.
Cancer Res 2009

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