SPOCD1 accelerates colorectal cancer by increasing the expression of YAP

Abstract Colorectal cancer (CRC) is a global disease, it is of great significance to discover a novel target for the treatment of CRC. SPOCD1 encodes proteins belonging to the transcription factor S-II (TFIIS) transcription factor family. The expression of SPOCD1 increases in a variety of tumor types, including ovarian cancer, osteosarcoma, glioblastoma, sophageal squamous cell carcinoma, and so on. In this study, we detected the expression of SPOCD1 in CRC tissues and cells. We also evaluated the correlation between the prognosis of CRC and the expression of SPOCD1 and found SPOCD1 was overexpressed in CRC and correlated with a poor prognosis. Meanwhile, the correlations between SPOCD1 expression and drugs were evaluated as well. We observed the genetic alteration status of SPOCD1 in CRC. Immune cell infiltration showed that there is a positive correlation between SPOCD1 expression and immune function. In vitro, SPOCD1 could promote CRC cell proliferation and migration. In the meantime, apoptosis was inhibited. YAP was identified as the target gene of SPOCD1 via qRT-PCR and western blot. Compared to only transfecting siSPOCD1, the proliferation of HT29 cells was partially restored when co-transfected with siSPOCD1 and oeYAP. Background: CRC is a common digestive tract tumor with the highest incidence in the world. SPOCD1 is a novel gene that encodes proteins belonging to the transcription factor S-II (TFIIS) transcription factor family. Up to now, whether SPOCD1 contributes the pathegenesis of CRC has been poorly defined. The main purpose of our research was to find the association between SPOCD1 and CRC. Methods: We used CRC datasets from the tumor immune estimation resource, version 2 (TIMER2) database, and immune cell infiltration was created to investigate immune cell dysregulation in CRC. Western blot was used to detect the expression of SPOCD1 in CRC and non-cancerous tissue. The expression of SPOCD1 in CRC cells was detected by real-time polymerase chain reaction and western blot. Cell Counting Kit 8 and colony formation assay analysis were conducted to analyze the effect of SPOCD1 on cell proliferation. And cell migration was analyzed by scratch assay. Using apoptotic proteins to assess the apoptotic capacity of cells. The protein expression of SPOCD1 and YAP in CRC cells was measured by Western blot. Results: SPOCD1 was overexpressed in CRC and correlated with a poor prognosis. The higher the expression of SPOCD1, the shorter the survival rate. The expression of SPOCD1 is increased in colorectal cancer cells such as HT29 and SW480 cells. What’s more, the reduction of SPOCD1 inhibits the proliferation and migration of HT29 and SW480 cells and increases apoptosis in HT29 and SW480 cells. And the Hippo/YAP pathway was inhibited by the knockdown of SPOCD1 in HT29 and SW480 cells. Conclusion: Our study suggests that SPOCD1 may play an oncogenic role by activating the Hippo/YAP pathway to inhibit apoptosis in CRC and can be a potential target for the treatment of CRC.