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Background: SOX2OT is a novel cancer associated long non-coding RNA (LncRNA) with higher expression in variable tumor tissues, including esophageal squamous cell carcinoma (ESCC). It also plays an important function in embryonic neuronal development. Regarding its function in both stemness and carcinogenesis, here, we aimed to investigate its expression and function in tumorspheres of the esophagus using the RNAi method. Material & Methods: Two esophageal squamous cancer cells (ESCC): KYSE30 and YM1 cells were used for sphere enrichment. Cells were transfected with SOX2OT targeting and control siRNA. The size and the number of spheres were measured using light microscopy. Gene expression of the pluripotency genes was measured by qRT-PCR and docetaxel chemoresistance was assessed by MTS viability assay. Results: Our findings showed that ESCC tumorspheres overexpress SOX2OT gene along with other stemness genes (SOX2, OCT4A, and Nanog) compared to their original cancer cells. RNAi experiments indicated that SOX2OT knockdown can suppress the stemness-related gene expression, sphere formation ability (both size and number), and docetaxel resistance as three of the main cancer stem cell characteristics of tumorspheres. Conclusion: Altogether our results showed the regulatory role of SOX2OT in pluripotency and stemness in ESCC tumorspheres. Our results suggest a potential application of SOX2OT inhibition in combination with docetaxel for ESCC inhibition in vitro.

Endoplasmic reticulum (ENR) stress perturbs cell homeostasis and induces the unfolded protein response (UPR). In breast cancer, this process is activated by oestrogen deprivation and is associated with tamoxifen resistance. We present evidence that the transcription factor SOX2 and the long noncoding RNA SOX2 overlapping transcript (SOX2OT) are upregulated in oestrogen receptor-positive (ER+) breast cancer and in response to oestrogen deprivation. We examined the effect of the UPR on SOX2 and SOX2OT expression and the effect of SOX2OT on UPR pathways in breast cancer cell lines. The induction of the UPR by thapsigargin or glucose deprivation upregulates SOX2OT expression. This upregulation is also shown with the anti-oestrogen 4OH-tamoxifen and mTOR inhibitor everolimus in ER + breast cancer cells that are sensitive to oestrogen deprivation or everolimus treatment. SOX2OT overexpression decreased BiP and PERK expression. This effect of SOX2OT overexpression was confirmed on BiP and PERK pathway by q-PCR. Our results show that a long noncoding RNA regulates the UPR and evince a new function of SOX2OT as a participant of ENR stress reprogramming of breast cancer cells.