Cancer-associated fibroblasts-derived extracellular vesicles carrying lncRNA SNHG3 facilitate colorectal cancer cell proliferation via the miR-34b-5p/HuR/HOXC6 axis.

Cancer-associated fibroblasts (CAFs)-derived extracellular vesicles (EVs) can mediate tumorigenesis. Long noncoding RNA (LncRNA) SNHG3 is implicated in colorectal cancer (CRC) progression. The current study sought to clarify the role of CAFs-EVs carrying SNHG3 in CRC cell proliferation. Firstly, CAFs and normal fibroblasts (NFs) were cultured and identified, followed by isolation and characterization of CAFs-EVs and NFs-EVs. CRC cells were cultured with CAFs-EVs or CAFs-EVs overexpressing SNHG3. The effects of SNHG3 on CRC cell proliferation was evaluated using CCK-8, colony formation, and EdU staining assays. The binding relationships among SNHG3, miR-34b-5p, and HuR were validated, in addition to analyzing the binding between HuR and HOXC6. Lastly, xenograft tumor model was established to verify the role of CAFs-EVs carrying SNHG3 in vivo. SNHG3 was highly expressed in CRC cells and CAFs-EVs, whereas CAFs-EVs facilitated CRC cell proliferation. Mechanically, CAFs-EVs carried SNHG3 into CRC cells to upregulate HuR expression by competitively binding to miR-34b-5p, promote the binding of HuR and HOXC6, and enhance HOXC6 transcription. miR-34b-5p over-expression or HOXC6 silencing annulled the effect of CAFs-EVs. SNHG3 carried by CAFs-EVs facilitated CRC proliferation via the miR-34b-5p/HuR/HOXC6 axis in vivo. Collectively, our findings indicated that CAFs-EVs carried SNHG3 into CRC cells to upregulate HuR expression by sponging miR-34b-5p and finally enhance HOXC6 transcription, thereby facilitating CRC cell proliferation.

Mesenchymal Stem Cell-derived Extracellular Vesicles Transmitting MicroRNA-34a-5p Suppress Tumorigenesis of Colorectal Cancer Through c-MYC/DNMT3a/PTEN Axis.

Mesenchymal stem cell-derived extracellular vesicles (MSC-EV) can transport microRNAs (miRNAs) into colorectal cancer (CRC) cells, thus to inhibit the malignant phenotype of cancer cells. Whether MSC-EV could deliver miR-34a-5p to suppress CRC development was surveyed through the research. miR-34a-5p, c-MYC, DNA methyltransferase 3a (DNMT3a), and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression were measured in CRC tissues and cell lines. miR-34a-5p and c-MYC expression were altered by transfection in HCT-116 cells. MSC-EV were transfected with miR-34a-5p- and c-MYC-related oligonucleotides and co-cultured with HCT-116 cells. HCT-116 cell growth after treatment was observed. Furthermore, the functional roles of miR-34a-5p and c-MYC were explored in vivo. The combined interactions of miR-34a-5p/c-MYC/DNMT3a/PTEN axis were assessed. miR-34a-5p and PTEN were downregulated while c-MYC and DNMT3a were upregulated in CRC. Depletion of miR-34a-5p drove while that of c-MYC restricted CRC cell growth. MSC-EV retarded CRC progression. Moreover, MSC-EV carrying overexpressed miR-34a-5p or depleted c-MYC further disrupted CRC cell progression. miR-34a-5p targeted c-MYC to regulate DNMT3a and PTEN. c-MYC overexpression abrogated EV-derived miR-34a-5p upregulation-induced effects on CRC. Restoring miR-34a-5p or depleting c-MYC in MSC-EV limited CRC tumor formation. MSC-EV-derived miR-34a-5p depresses CRC development through modulating the binding of c-MYC to DNMT3a and epigenetically regulating PTEN.

LINC01089 blocks malignant progression of thyroid cancer by binding miR-27b-3p to enhance the FBLN5 protein level.

LINC01089 suppresses the malignant progression of breast, colorectal, and non-small cell lung cancers. However, the function of LINC01089 in thyroid cancer has not yet been elucidated. Here, The Cancer Genome Atlas (TCGA) database showed that LINC01089 expression is remarkably reduced in thyroid cancer tissues. Lower LINC01089 expression was correlated with higher tumor stage and regional lymph node metastasis. Furthermore, LINC01089 overexpression effectively blocked thyroid cancer cell proliferation, migration, and invasion. LINC01089 acted as a competing endogenous RNA for miR-27b-3p, thus inhibiting miR-27b-3p expression. miR-27b-3p overexpression promoted the proliferation, migration, and invasion of thyroid cancer, reversing the effect of LINC01089 overexpression on thyroid cancer. Fibulin-5 (FBLN5) was discovered as a target of miR-27b-3p in thyroid cancer. FBLN5 expression was found to be underexpressed in thyroid cancer and was enhanced and reduced by LINC00987 overexpression and miR-27b-3p overexpression, respectively. Furthermore, FBLN5 knockdown promoted the malignant progression of thyroid cancer cells by counteracting the effect of LINC00987. In conclusion, LINC01089 plays a tumor-suppressive role by binding miR-27b-3p to increase FBLN5 expression, confirming that LINC01089 has tremendous potential to become a therapeutic target for thyroid cancer treatment.

Efficacy of conversion surgery after neoadjuvant intraperitoneal-systemic chemotherapy in treating peritoneal metastasis of gastric cancer.

PURPOSE: To explore the effectiveness and safety of conversion surgery after neoadjuvant intraperitoneal-systemic chemotherapy (NIPS) in treating gastric cancer patients with peritoneal metastasis. METHODS: 80 patients definitely diagnosed with peritoneal metastasis of gastric cancer treated in our hospital from March 2016 to September 2017 were evaluated. All the patients were randomly assigned into two groups and received oral administration of S-1 + intravenous and intraperitoneal chemotherapy with paclitaxel or oral administration of S-1 + intravenous chemotherapy with oxaliplatin, with 40 patients in each group. Following NIPS conversion therapy, the patients with indications for surgery underwent radical gastrectomy. The short-term efficacy of chemotherapy and incidence of chemotherapy-related adverse reactions were compared between the two groups. The surgical methods, intraoperative conditions (lymph node dissection and surgical margins) and postoperative complications were recorded in the two groups of patients, and the survival in the two groups was recorded via follow-up. RESULTS: The efficacy was evaluated for all the patients after 4 cycles of treatment. The median cycles of chemotherapy was 6.9 in NIPS group, with a response rate of 85.0% (34/40), while it was 6.4 cycles in control group, with a response rate of 70.0% (28/40). The overall response rate (ORR) after chemotherapy in NIPS group was notably higher than in control group (p=0.041). After chemotherapy, radical gastrectomy was performed in 40 patients with surgical indications, including 22 cases of R0 resection, 10 cases of R1 resection and 8 cases of R2 resection. Some patients developed postoperative complications, including 1 case of incision infection, 3 cases each of ileus and intra-abdominal hemorrhage, 2 cases each of peritonitis and pancreatic fistula, and 4 cases of anastomotic fistula. All the patients were followed up for 2-18 months, and the median follow-up time was 14.1 months in NIPS group and 13.3 months in control group. The median overall survival (mOS) was 13.4 months in NIPS group and 10.8 months in control group. CONCLUSION: NIPS combined with radical gastrectomy has definite efficacy in treating gastric cancer patients with peritoneal metastasis and cause tolerable adverse reactions, and it can significantly raise the patient survival compared with systemic chemotherapy alone.

Topical application of temperature-sensitive caerin 1.1 and 1.9 gel inhibits TC-1 tumor growth in mice.

Genital warts, which are one of the most common sexually transmitted diseases (STDs), result from persistent infection with human papillomavirus (HPV), especially subtypes 6 or 11. Topical application of 5% imiquimod cream is currently recommended as a first-line treatment choice for genital warts, but the clearance and patient compliance rates remain less than sufficient. In the current study, we developed a temperature-sensitive gel that contains the host-defense peptides caerin 1.1 and 1.9, which were originally isolated from Australian tree frogs of the genus Litoria. Growth of HPV16 E6/E7-transformed TC-1 cells was inhibited in vitro and in vivo following injection of the tumor with the caerin gel in a TC-1 tumor mouse model. Furthermore, when the caerin gel was topically applied, the inhibitory effect remained, and T, NK cells were attracted to the tumor site. In addition, the gel maintained a similar level of bioactivity after incubation at room temperature for 30 days. Our results suggest that this caerin gel, following further optimization, may provide an alternative method for the management of genital warts.

Human papillomavirus infection among head and neck squamous cell carcinomas in southern China.

Human papillomavirus (HPV) related tumours account for a significant proportion of head and neck squamous cell carcinomas (HNSCCs) in developed countries. They respond better to chemo- and radio-therapy, and have a better stage specific prognosis. To establish their prevalence in China, we assessed a series of histology confirmed HNSCCs collected in Zhejiang and Guangdong provinces by PCR for HPV DNA and by immunohistochemistry for p16 protein status. Among 303 HNSCCs, HPV DNA was detected in 26.4%, with HPV16 DNA in 71% of these. Of HNSCC located in the oropharynx, 38.55% (32/83) were HPV+ve. In this series, p16 status was a relatively poor predictor of HPV status as detected by PCR. The stage specific survival time of HPV+ HNSCCs was significantly longer than for HPV- HNSCC. HPV status should be assessed for oropharyngeal cancers in China to assist with appropriate management, and prophylaxis against HPV infection should be considered to reduce the incidence of this disease.