Long noncoding RNA HOTAIR knockdown inhibits autophagy and epithelial-mesenchymal transition through the Wnt signaling pathway in radioresistant human cervical cancer HeLa cells
Authors: Sihong Guo
Jie Chen
Hongqi Xiao
Ge Lou
Xinggang Guo
Jing Li
Yuxia Wang
Journal: Journal of Cellular Physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: HOTAIR; Wnt signaling pathway; autophagy; cervical cancer; epithelial-to-mesenchymal transition (EMT)
Affiliations: Department of General surgery, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China., Department of Clinical Chinese Medicine Integrative With Western Medicine, International Education College, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China., Department of Gynecology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.

Abstract:  Cervical cancer is one of the most common female malignancies around the world, and radiation resistance is a major obstacle to cancer therapy. Previously, overexpression of the long noncoding ribonucleic acid (RNA) (lncRNA) HOX transcript antisense RNA (HOTAIR) has been found to be associated with the invasion and metastasis capacities of several epithelial cancers, including cervical cancer. To gain insights into the molecular mechanisms of HOTAIR in cervical cancer resistance to radiotherapy, we investigated cellular autophagy and epithelial-to-mesenchymal transition (EMT) in radioresistant human cervical cancer HeLa cells when HOTAIR was suppressed. HOTAIR levels were quantified in cancerous and noncancerous cervical tissues obtained from 108 patients with cervical cancer. Next, we inhibited HOTAIR by RNA interference and activated the Wnt signaling pathway by LiCl in radioresistant HeLa cells to investigate the regulatory mechanisms for the HOTAIR mediating Wnt signaling pathway. We determined that the upregulated HOTAIR may contribute to cervical cancer progression. We found that the short interfering ribonucleic acid (siRNA)-mediated knockdown of HOTAIR disturbed the Wnt signaling pathway, reduced autophagy, inhibited EMT, decreased cell proliferation, and induced apoptosis in radioresistant HeLa cells. It is worthy to note that the combination treatment of siRNA-HOTAIR and LiCl demonstrated that the activation of the Wnt signaling pathway is responsible for the beneficial effect of HOTAIR knockdown in enhancing sensitivity to radiotherapy in radioresistant HeLa cells. Together, our results revealed an important role of HOTAIR in regulating cervical cancer resistance to radiotherapy. Functional suppression of HOTAIR could enhance sensitivity to radiotherapy by reduction of autophagy and reversal of EMT through the suppression of the Wnt signaling pathway. 

Retracted: Yes

PubPeer comments:
  FIGURE 10 HOTAIR knockdown induces cell apoptosis through negative regulation of the Wnt signaling pathway in radioresistant HeLa cells. (a) Flow cytometry .  This is one of a long series of  sneezing dust bunnies flow-cytometry figures in the lncRNA literature. For comparison, Fig 6A of [Zhu et al (2018)] , with many other manifestations in that thread.  , 
 Retracted [20 July 2021] . ---------------------------------------------- The above article, published online on 26 October 2018 in Wiley Online Library , has been retracted by agreement between the journal s Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. As several flaws and inconsistencies between results presented and experimental methods described were found, the editors consider the conclusions of this article to be invalid. ,