MicroRNA-301a modulates doxorubicin resistance in osteosarcoma cells by targeting AMP-activated protein kinase alpha 1
Authors: Shiqing Feng
Guoqing Duan
Yuanmin Zhang
Journal: Biochemical and Biophysical Research Communications (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: AMPKα1; Doxorubicin; Drug resistance; HMGCR; MicroRNA-301a
Affiliations: Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin 300052, PR China; Department of Joint and Sports Medicine, Affiliated Hospital of Jining Medical College, Jining 272029, PR China., Department of Joint and Sports Medicine, Affiliated Hospital of Jining Medical College, Jining 272029, PR China., Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin 300052, PR China. Electronic address: .

Abstract:  MicroRNAs have been implicated in drug resistance of osteosarcoma (OS). MicroRNA-301a (miR-301a) is up-regulated and functions as an oncogene in various cancers. However, little is known about the role of miR-301a in drug resistance of OS cells. In this study, we found that doxorubicin induced time-dependent expression of miR-301a in OS cells. Meantime, doxorubicin promoted HMGCR expression and inhibited AMPKα1 expression, which was further facilitated by miR-301a overexpression. Luciferase reporter assay identified AMPKα1 as direct target gene of miR-301a. Notably, miR-301a reduced doxorubicin-induced cell apoptosis whereas anti-miR-301a enhanced apoptosis in OS cells, suggesting that up-regulation of miR-301a contributed to chemoresistance of OS cells. Consistently, our data showed that miR-301a and HMGCR were up-regulated in chemotherapy-resistant OS compared to those in control OS. Our findings suggested that miR-301a might be a potential biomarker for chemotherapy-resistant OS and a promising therapeutic target for overcoming drug resistance of OS. 

Retracted: No

PubPeer comments:
 (a) According to the context, the terms $tilde{z}$ and $tilde{x}_i$ in eq.(6) are intervals. As a result, it seems that the term $tilde{P}$ defined in eq.(7) is also an interval, although the utility function is introduced in the context as a real valued function. However, the term $tilde{P}$ defined by eq.(7) is not sound. It may not even be a positive interval according to the operations provided in the paper. According to Definition 2, it follows that $$[1,2] [1,2] + [1,2] [1,2] -2 =[0.5,2]+[0.5, 2] -2 =[-1,2]$$ However, the nonnegative intervals are considered throughout this paper as claimed by the authors, which is also a requirement for the operations in Definition 2. **The result in eq.(7) is confusing.** (b) Moreover, the authors claimed that the term $tilde{P}$ defined in eq.(7) is u201cthe deviation between $tilde{z}$ and $u(tilde{x}_i)$u201d. Since $tilde{P}$ could have a negative left endpoint as just illustrated, **the u201cdeviationu201d to be minimized in eq.(7) is not well justified.** (c) **The result in eq.(8) is even more confusing**. Since the arguments involved are intervals and the function to be minimized is also interval valued, **it is not a trivial issue to define properly the meaning of an optimal solution.** However, the authors presented eq.(8) by claiming u201c**according to the necessary condition of extreme value**u201d. **The claimed u201cnecessary condition of extreme valueu201d is not clear in this context and may not exist without defining the optimality.** Could the authors address these issues, for instance, the necessary condition of extreme value for interval scenarios? ![file] ![file] , 
 The authors claimed that eq.(7) measures the u201cdeviationu201d between two intervals. However, such a formulation is not sound even for the trivial case according to the operations defined in Definition 2. For example, let $n=1$, $lambda=1$, $$u(tilde{z}) =[1,2]$$ and $$u(tilde{x})=[1,2]$$ According to eq.(7), it follows that $$[1,2] [1,2] + [1,2] [1,2] -2 =[0.5,2]+[0.5, 2] -2 =[-1,2]$$ It is not clear why and how the interval $[-1,2]$, which is not even positive, measures the deviation between $[1,2]$ and $[1,2]$. Considering the critical role of eq.(7) played in this paper, could the authors address this issue? ![file] ![file] ,