Ovarian cancer proliferation and apoptosis are regulated by human transfer RNA methyltransferase 9-likevia LIN9
Authors: Jia Wang
Huai Mei Chen
Ying Feng Zhang
Yan Hong Gao
Journal: Oncology Letters (2017)
Discipline: CLINICAL MEDICINE
Keywords: HO8910PM cells; apoptosis; human transfer RNA methyl transferase 9-like; ovarian cancer.
Affiliations: Department of Obstetrics and Gynecology, University-Town Hospital of Chongqing Medical University, Chongqing 401331, P.R. China.

Abstract:  Current traditional treatment options have little impact on the long-term survival of patients with ovarian cancer due to a lack of understanding of the molecular transformations that occur in ovarian carcinoma. Transfer RNAs (tRNAs) perform a key role in protein translational fidelity. Enzymes involved in tRNA modification may function as regulators of cancer progression. Human tRNA methyltransferase 9-like (hTRM9L) catalyzes tRNA wobble base modifications, which regulate ovarian cancer growth and apoptosis via the retinoblastoma protein (pRB) and p53 signaling pathways. The aim of the present study was to confirm the role of hTRM9L in the proliferation and apoptosis of ovarian cancer. Immunohistochemistry was performed to investigate the expression of hTRM9L and LIN9 in 70 ovarian tissues. hTRM9L was amplified by polymerase chain reaction (PCR) and inserted into the Ubi-multiple cloning site-enhanced green fluorescent protein (EGFP)-internal ribosome entry site-puromycin lentiviral expression vector to create the Ubi-KIAA1456-EGFP-puromycin (LV-KIAA1456) vector. The lentiviruses were subsequently compounded and transduced into HO8910PM cells. hTRM9L, LIN9 and B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X protein (Bax) expression levels were examined by PCR and western blot analysis. Apoptosis was verified by flow cytometry, and cell proliferation was evaluated using Cell Counting Kit-8. hTRM9L and LIN9 expression were reduced in the ovarian cancer group, and there was a positive correlation between hTRM9L and LIN9 expression according to Pearson's correlation coefficient (r=0.406; P&lt;0.05). hTRM9L was increased by 2-3-foldin HO8910PM cells following LV-hTRM9L transduction. The expression of hTRM9L at the mRNA and protein levels in HO8910PM cells that were transfected with LV-hTRM9L was significantly increased compared with the negative control, as confirmed by reverse transcription-quantitative PCR and western blot analysis, respectively (P&lt;0.05). The same was observed for LIN9 and Bax (P&lt;0.05). By contrast, Bcl-2 was downregulated in LV-hTRM9L (P&lt;0.05). Furthermore, cell growth was inhibited (P&lt;0.05) and apoptosis increased (P&lt;0.05). In the present study, hTRM9L was shown to prevent tumor growth and promote apoptosis by regulating LIN9, which is associated with the pRB and p53 signaling pathways. This maybe a novel breakthrough in the treatment of ovarian cancer. 

Retracted: No

PubPeer comments:
 Figure 1. * Blue boxes: The left-most hTRM9L and LIN9 panels appear to show an area of overlap. ![file] , 
 COrrigendum. [12 January 2021] . ----------------------------------- Following the publication of the above paper, an interested reader drew to the authorsu2019 attention that, in Fig. 1 on p. 4464, the left-most hTRM9L and LIN9 panels (representing the data from ovarian cancer tissues at u00d7200 magnification) appeared to show an area of overlap. The authors were able to consult their original data, and realized that the Figure had been compiled incorrectly; essentially, the wrong image was chosen for the LIN9 panel. The revised version of Fig. 1, showing the correct data for the abovementioned panel, is shown below. This error did not have a significant impact on the results or the conclusions reported in this study. The authors are grateful to the Editor of Oncology Letters for allowing them the opportunity to publish this Corrigendum, and all of the authors agree to the publication of this Corrigendum. The authors sincerely apologize for this mistake, and regret any inconvenience this mistake has caused. ![] , 
 Thank you for the update, Hoya. I was the  interested reader and reported this concern to the journal publisher (Spandidos) in August 2020. However, I was not notified about this correction. ,