miR‑222 regulates sorafenib resistance and enhance tumorigenicity in hepatocellular carcinoma
Authors: Kai Liu
Songyang Liu
Yingchao Wang
Wei Zhang
Bai Ji
Yahui Liu
Journal: International Journal of Oncology (2014)
Discipline: CLINICAL MEDICINE
Keywords: miR-222 cluster; oncomiR; hepatocellular carcinoma; chemotherapy drug resistance; liver tumorigenicity
Affiliations: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun, Jilin Province, P.R. China.

Abstract:  The miR‑222 cluster has been demonstrated to function as oncomiR in human hepatocellular carcinoma (HCC). miR‑222 confers chemotherapy drug resistance in various cancers, including HCC. However, the effects and mechanisms by which miR‑222 regulates liver tumorigenicity and confers sorafenib (SOR) resistance remain unclear. Here we first investigated the miR‑222 effect on proliferation, cell cycle, apoptosis, migration and invasion of HCC. Our results demonstrated that miRNA inhibitors specially targeting miR‑222 significantly suppressed cellular proliferation, migration, invasion and G1/S transition of the cell cycle, and induced cell apoptosis in HepG2 cells. In addition, we investigated whether miR‑222 confers SOR resistance in HepG2 cells to explore it roles in acquisition of drug resistance. The results showed that miR‑222 inhibitors induced sensitivity to the antitumor effect of sorafenib in human HepG2 cells. Importantly, our study also showed that miR‑222 could regulate the expression of phosphorylation PI3K and AKT, which might contribute to miR‑222 conferred SOR resistance in HepG2 cells. In conclusion, this study demonstrates that miR‑222 can promote cell proliferation, migration and invasion, and decrease cell apoptosis, as well as enhance the resistance of HCC cells to sorafenib miR‑222 through activating the PI3K/AKT signaling pathway. 

Retracted: Yes

PubPeer comments:
 Figs 3C, 7. The protein blob marked with an orange rectangle seems to be present in both. ![file] Red, brown, light orange, green, rose rectangles mark unexpected similarities to Figs 2C *[left]* and 5 *[right]* of [Liu et al (2014)] . ![file] For further comparison: Figs 4C, 5D from [Zhang et al (2014)] . ![file] , 
 #1 Figs 3C and 7 again... ![] and Figs 4C, 5D from [Zhang et al (2014)] ... ![] ...this time for comparison with the bands of Fig 5C, [Li et al (2014)] . ![] , 
 Clockwise from top left: - Fig 3A from [Liu et al (2015)] .  Effects of miR-222 inhibitor on HepG2 cell cycle distribution. (A) Cell DNA content distribution in each phase. - Fig 3A from [Zhang et al (2015)] .  Effects of microRNA-145 (miR-145) on multiple myeloma (MM) cell cycle distribution. (A) Cell DNA content distribution in each phase. - Fig 3A from [Li et al (2015)] .  Enforced expression of miR-338-3p induced cell cycle distribution and cell apoptosis in EC9706 cells. (A) Cell DNA content distribution in each phase. - Fig 3A from [Zhang et al (2015b)] ,  miR-137 induces changes in cell cycle distribution and cell apoptosis in SKOV3 cells. (A) Cell DNA content distribution in each phase ![file] The same panels keep appearing. , 
 *[left]* Fig 2A from [Liu et al (2015)] .  Effect of DOX and Ad sh-NOB1 alone or in combination on cell cycle of TPC-1 cells. (A) Cell DNA content distribution in each phase . *[upper right]* Fig 2C from [Song et al (2015)] .  Determination of HeLa cell cycle distribution by PI staining after transfection with miR-133a or miR-Ctrl . *[lower right]* Fig 2d from [Zhang et al (2015)] .  The cell cycle was detected by PI staining after being transfected with miR-133a or miR-NC. ![file] The same panels keep appearing. --------------------------------------------------- Clockwise from upper left: - Fig 2D from [Pang et al (2015)] .  cell cycle progression ... determined in HepG2 cells transfected with the miR-154 mimic or miR-NC. - Fig 2D from [Zhao et al (2017)] .  cell cycle stage ... assessed in MM1S cells transfected with miR-144-3p mimic or miR-NC. - Fig 2D from [Li et al (2016)] .  The cell cycle procession was detected by flow cytometry after transfection with miR-494 or miR-NC . - Fig 2C from [Luan et al (2015)] .  Cell cycle was measured in glioma cells at posttransfection by flow cytometry . ![file] The same panels keep appearing. --------------------------------- Fig 2D from [Zhou et al (2016)] .  Cell cycle distribution of U2OS cells transfected with the miR-154 mimic was determined by flow cytometry . ![file] , 
 Retracted [1 November 2021] . ---------------------------- Following the publication of this paper, it was drawn to the Editorsu2019 attention by a concerned reader that the flow cytometric data in Fig. 3A and western blotting data featured in Figs. 3C and 7 were strikingly similar to data appearing in different form in other articles that shared some of the same authors. Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, elsewhere prior to its submission to *International Journal of Oncology*, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. ,