<p>Long Non-Coding RNA PVT1 Regulates BAMBI To Promote Tumor Progression In Non-Small Cell Lung Cancer By Sponging miR-17-5p</p>
Authors: Zhao Wang
Feng Shao
Qiang Zhang
Yungang Sun
Journal: OncoTargets and Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: BAMBI; PVT1; miR-17-5p; non-small cell lung cancer; tumor progression.
Affiliations: Department of Thoracic Surgery, The Nanjing Chest Hospital, Nanjing, Jiangsu, People's Republic of China.

Abstract:  Background: Non-small cell lung cancer (NSCLC) is a common malignancy over the world. Previous report indicated that the plasmacytoma variant translocation 1 (PVT1) has been documented to function as an oncogene in various types of human cancers. However, the biological mechanism of PVT1 was still rarely reported in NSCLC. Methods: The levels of PVT1, miR-17-5p, and bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) in NSCLC tissues (n=64) and cells (H1299 and A549) were detected by qRT-PCR and immunohistochemistry (IHC). The protein level of BAMBI was measured by Western blot assay. Cell viability and apoptotic rate were evaluated by MTT assay and flow cytometry, respectively. The migrated and invaded abilities were assessed by Transwell assay and Wound healing assay. The interactions between miR-17-5p and PVT1 or BAMBI were predicted by starBase v2.0 and TargetScan, respectively, and then dual-luciferase reporter assay and RNA pull-down assay were performed to verify these interactions. The mice model experiments were constructed to further validate the roles of PVT1 in vivo. Results: The levels of PVT1 and BAMBI were both apparently increased, and miR-17-5p was declined in NSCLC tissues and cells. The depletion of PVT1 or BAMBI blocked cell viability, migrated and invaded abilities but impelled apoptotic rate in A549 and H1299 cells. PVT1 was validated as a sponge to miR-17-5p and BAMBI was a direct target of miR-17-5p. PVT1 promoted cell viability, migrated and invaded abilities but repressed apoptotic rate by targeting BAMBI. MiR-17-5p regulated cell behaviors mediated by PVT1. PVT1 silencing decreased BAMBI expression by sponging miR-17-5p. In addition, PVT1 knockdown blocked the xenograft tumor growth in vivo. Conclusion: These results manifested that PVT1 modulated BAMBI to promote tumor progression in NSCLC by sponging miR-17-5p. Thus, the novel regulatory pathway may provide a new therapeutic target for NSCLC patients. 

Retracted: No

PubPeer comments:
 Figure 4. Expression profile of select miRNAs and their corresponding target genes in HR and ZS cotton plants following whitefly infestation. (Au2013F) The histograms and associated lines indicate the relative abundance of the individual miRNAs and their corresponding targets, respectively. The left and middle panels correspond to the expression profiles of the indicated transcripts in HR and ZS plants infested with whiteflies at different time points, respectively. The T-plots in the right panel show the relative abundance of the degradation signal mediated by the miRNAs. The associated miRNA:mRNA duplex alignment is shown above each panel. The G-U pairs are indicated with an u2018ou2019 and mismatch base pairs are indicated with an u2018xu2019. ![file] Figure 4 appears to have an unusual duplication of counts , 
 Dear Archimonocelis Crucifera, Thanks again for the comment regarding the Figure 4 of this publication. We have checked it carefully and realize that you are right! We do use the same Figure 4B and 4E by mistake! We realized that the Degradome sequencing results of Figure 4B and 4E were repeated in the process of combining different images when we submit to the IJMS. As you can see, we used the right images in our previous submission to Plant Biotechnology Journal (Figure 7) for review and the PBJ editor send it our for peer-review but rejected it (All the reviewers and editors did not question this Figure 7 at that time). Then we submitted it to IJMS for review and finally get acceptance. During the revision process, we made this unpremeditated mistake caused the wrong combination of images, but it does not affect the conclusion in our article. Because the miR164 target gene is position 652 of NAC100 (Gh_A12G1620), the qRT-PCR primer is designed according to the flank sequence of NAC100 cleavage site (please see Table S1:P121~miR164~Gh_A12G1620). The T-plot of degradome sequencing error (Figure 4B, middle panel) was shown as miR390 target. Therefore, the expression of miR164 and NAC100 was not affected during cotton response to whitefly infestation. After a comprehensive analysis of our data, we made the conclusion with the miR390 regulating the development and resistance to whitefly in cotton. In fact, we did not change any descriptions in the main text regarding the Fig 4E when we submitted to IJMS from the rejected version of PBJ manuscript. Therefore, all the data explaining in this part of IJMS version is based on the right Fig 4E version shown in our previous submission and the replaced right Fig 4E will not affect the conclusion in our article. In the IJMS proofreading version, as you can see that the resolution of Figure 4 is not very high and again we missed the chance to correct this mistake. Now, we are contacting with the publisher and require the correction for this Figure. The Figure 4B degradome sequencing of plot will be replaced by miR164-NAC100 result (Figure 4_Corrected.png). All supplementary files are available on this website . Again, We sincerely appreciated you to point out this mistake and avoid the greater negative effects in the future of this publication. Regards Jianying Li ![file] ![file] ![file] ![file] ![file] , 
 Hi Jianying, thanks for the quick reply - can you post the counts versus position from the SRA data for those two graphs? , 
 Hi Jianying - thank you again for the very quick response. It is great you can correct the error. :0) - If higher resolution images can be made it would improve the manuscript! , 
 #3 Dear Natronorubrum , Thanks for the comment regarding the Figure 4 of this publication. The degradome sequencing (SRA accession: SRR3105380 ) was used to identify miRNA targets. The clean reads of degradome sequencing were mapped to the G. hirsutum transcriptome. Then, CleaveLand software (p 0.05) was used to detect putative miRNA targets cleavage site and abundance. If you have any more questions , plz feel free to contact with me. Regards, Jianying , 
 #4 Dear Archimonocelis Thanks for your quick and positive response regarding the Figure 4 of this publication. As your suggestion, we have uploaded all the high resolution images with more than 600dpi. The vector images and other data are available on my website . Thank you again for your suggestions to further improve the quality of the manuscript. Regards, Jianying ![file] ![file] ,