Involvement of miR-619-5p in resistance to cisplatin by regulating ATXN3 in oral squamous cell carcinoma
Authors: Xiaomeng Song
Enshi Yan
Junbo Zhou
An Song
Wei Zhang
Xueming Yang
Hongxia Zhu
Jie Liu
Yuanyuan Wu
Weiming Chu
Yunong Wu
Yang Zheng
Zaiou Zhu
Jinhai Ye
Xu Ding
Journal: International journal of biological sciences (2021)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: ATXN3; OSCC; cisplatin-resistance; miR-619-5p.
Affiliations: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China., Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China., Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, People's Republic of China., Department of Stomatology, the Affiliated People's Hospital of Jiangsu University, Zhenjiang 21200, Jiangsu Province, China., Department of Anesthesiology, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China., Department of Stomatology, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Nanjing, Jiangsu, People's Republic of China.

Abstract:  MicroRNAs are major post-transcriptional regulators responsible for the development of human cancers, including OSCC. The specific role of miR-619-5p in OSCC, however, is rarely reported. Cisplatin is one of the mostly applied chemotherapy drugs of OSCC. Nevertheless, drug resistance of cisplatin following the initial chemotherapy largely restricts its clinical benefits, and the mechanism of cisplatin resistance is unclear. This study intends to explore the biological function of miR-619-5p in the development of cisplatin resistance in OSCC cell lines and a xenograft model, as well as the potential molecular mechanism. Our results showed that miR-619-5p was down-regulated in OSCC samples and cisplatin-resistant OSCC cells. Ectopically expressed miR-619-5p inhibited proliferative, migratory and invasive abilities of OSCC cisplatin-resistant cells. The putative target gene ATXN3 was predicted by bioinformatic analysis and confirmed by dual-luciferase reporter assay. Importantly, ATXN3 was responsible for the regulatory effects of miR-619-5p on biological behaviors of cisplatin-resistant OSCC cells. Moreover, miR-619-5p mimics and ATXN3-siRNA significantly enhanced ATXN3 knockdown in both HN6/CDDPR and CAL27/CDDPR cells and inhibited expression of PI3K and AKT. In vivo evidences demonstrated that intratumoral injection of miR-619-5p agomir remarkably slowed down the growth of OSCC in xenograft mice. Collectively, microRNA-619-5p was the vital regulator for regulating cisplatin resistance of OSCC, which may be served as a potential therapeutic target. 

Retracted: No

PubPeer comments:
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 I was Peer 1 above. Here is a redo of Figure 1C, where I also noted a region of inverse symmetry in the  Semi-native lane, marked in yellow. ![file] , 
 Figure 1B: * Pink boxes: The first three lanes in the Actin probe blot look very similar. A vertical light line is visible in two of them, but the rest of the lanes look remarkably similar. Image made a bit lighter to bring out details. ![file] , 
 Figure 3. * Orange boxes: Two panels in A) appear to overlap, but this might be acceptable if these are just showing two different fields of the same specimen * Cyan boxes: Two panels in C) appear to share the same top left area ![file] , 
 #3 #3 So far what I can recall is that the position showed by arrow was as it is. Some noise might be polished. Afterall we tried to show the position of the bands is Western blot and scientifically it was perfect. , 
 #5 You might be right. , 
 #4 So far what I can recall that the actin probe generated very faint signal. We tried to improve the contrast. Our target gene expression was perfect and no band in untransformed and band in Line 1-3 can justify our statement. As it was done more than 10 years before, we can not trace the autoradiogram. No scientific error was involved there. , 
 Thank you for your comments. ,